[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-lung-non-small-cell-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-lung-non-small-cell-carcinoma":716},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,26,0,25,[9,44,68,94,115,137,246,316,336,352,381,399,420,442,480,498,518,554,584,603,622,640,657,679,698],{"id":10,"slug":4,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":32,"lastUpdatePostDateStruct":33,"startDateStruct":36,"completionDateStruct":38,"leadSponsor":40,"locationsCount":43},"100554545",false,"NCT06500481","Testing Proton Craniospinal Radiation Therapy Versus the Usual Radiation Therapy for Leptomeningeal Metastasis, RADIATE-LM Trial","A Phase III Randomized Clinical Trial of Proton Craniospinal Irradiation Versus Involved-Field Radiotherapy for Patients With Breast Cancer or Non-Small Cell Lung Cancer Leptomeningeal Metastasis (Radiate-LM)","Inclusion Criteria:\n\n* PRIOR TO STEP 1 REGISTRATION\n* Patients with pathologically (histologically or cytologically) proven diagnosis of breast cancer or NSCLC\n* Patients must have newly diagnosed leptomeningeal metastasis established through at least one of the following:\n\n  * Positive CSF cytology for malignancy\n\n    * CSF cytology with suspicious cells is considered positive; CSF cytology with atypical cells is considered equivocal and not positive\n  * Patients with an equivocal or negative CSF cytology result, or not suitable for CSF sampling, radiographic diagnosis of leptomeningeal metastasis with linear and\u002For nodular disease and documentation of typical clinical signs (European Association of Neuro-Oncology \\[EANO\\]-European Society for Medical Oncology \\[ESMO\\] Diagnostic Criteria Type IIA-IIC) is required\n\n    * Patients with typical clinical signs of leptomeningeal metastasis may have one or more of the following symptoms and signs: headache, nausea, vomiting, mental status change, gait difficulty, cranial nerve palsy, diplopia, visual change, hearing loss, radicular weakness, radicular sensory change, urinary retention, saddle anesthesia, constipation, neck pain, and back pain\n  * For patients with prior history of immunotherapy or current immunotherapy, CSF sampling rather than just MRI enhancement is strongly recommended to exclude immune-related aseptic meningitis\n* Patients must be candidates for radiation therapy for the treatment of leptomeningeal metastasis\n* Age ≥ 18\n* PRIOR TO STEP 2 REGISTRATION\n* Note: Step 2 registration must occur no later than 30 calendar days after step 1 registration\n* Financial clearance for proton therapy treatment\n* Patients must have systemic disease evaluation through standard of care imaging for example CT chest\u002Fabdomen\u002Fpelvis or body PET\u002FCT\n* Karnofsky performance status ≥ 60\n* Not pregnant and not nursing\n\n  * Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal\n* Hemoglobin ≥ 8.0 g\u002Fdl (Note: The use of transfusion or other intervention to achieve hemoglobin \\[Hgb\\] ≥ 8.0 g\u002Fdl is acceptable)\n* Absolute neutrophil count (ANC) ≥ 1,000\u002Fmm\\^3 (Note: the use of granulocyte-colony stimulating factor or other intervention to achieve ANC ≥ 1,000\u002Fmm\\^3 is acceptable)\n* Platelets ≥ 100,000\u002Fmm\\^3 (Note: the use of transfusion or other intervention to achieve platelets ≥ 100,000\u002Fmm\\^3 is acceptable)\n* Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (patients with known Gilbert disease without other clinically significant liver abnormalities are not excluded)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine transaminase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 × ULN\n* No prior radiation therapy to the spinal cord with equivalent dose in 2 gray (Gy) fractions (EQD2) more than 40Gy or cauda equina with EQD2 more than 50Gy using alpha\u002Fbeta ratio of 3\n* No prior treatment for leptomeningeal metastasis (note: prior CNS treatment for other non-leptomeningeal disease is allowed)\n* No history of unstable angina requiring hospitalization in the last 3 months\n* No history of myocardial infarction within the last 3 months\n* New York Heart Association Functional Classification II or better (New York Heart Association \\[NYHA\\] Functional Classification III\u002FIV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)\n* No active infection currently requiring intravenous (IV) antibiotic management\n* No active chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy\n* No CTCAE v5.0 ≥ grade 2 encephalopathy","ALL","18 Years",{"count":19,"type":20},115,"ESTIMATED","INTERVENTIONAL",[23],"PHASE3","This phase III trial compares proton craniospinal irradiation (pCSI) to involved-field radiation therapy (IFRT) for the treatment of breast or non-small cell lung cancer that has spread from where it first started to the cerebrospinal fluid filled space that surrounds the brain and spinal cord (leptomeningeal metastasis). Patients with leptomeningeal metastasis (LM) may develop multiple areas of nervous system (neurologic) impairment that can be life-threatening. Radiation therapy (RT) effectively relieves local symptoms due to LM. RT uses high energy radiography (x-rays), particles, or radioactive seeds to kill cancer cells and shrink tumors. IFRT is commonly used to treat symptoms of LM. IFRT is radiation treatment that uses x-rays to treat specific areas of LM and to relieve and\u002For prevent symptoms. pCSI uses protons that can be directed with more accuracy than x-rays which allows treatment of the entire central nervous system space containing the cerebrospinal fluid (CSF), brain, and spinal cord. The pCSI treatment could delay the worsening of LM. Giving pCSI may be better than IFRT in treating LM in patients with breast or non-small cell lung cancer.",[26,27,28,29,30],"Anatomic Stage IV Breast Cancer AJCC v8","Metastatic Breast Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Malignant Neoplasm in the Leptomeninges","Stage IV Lung Cancer AJCC v8","RECRUITING","2026-06-22",{"date":34,"type":35},"2026-06-25","ACTUAL",{"date":37,"type":35},"2025-03-04",{"date":39,"type":20},"2028-07-31",{"name":41,"class":42},"NRG Oncology","OTHER",58,{"id":45,"slug":4,"hasResults":11,"nctId":46,"briefTitle":47,"officialTitle":48,"acronym":4,"eligibilityCriteria":49,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":50,"targetDuration":4,"studyType":21,"phases":52,"briefSummary":53,"conditions":54,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":32,"lastUpdatePostDateStruct":61,"startDateStruct":62,"completionDateStruct":64,"leadSponsor":66,"locationsCount":67},"100554543","NCT06500455","Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain","Phase III Trial of Single Fraction Stereotactic Radiosurgery (SRS) Versus Fractionated SRS (FSRS) for Intact Brain Metastases","Inclusion Criteria:\n\n* Pathologically (histologically or cytologically) proven diagnosis of one of the following solid tumor malignancies within 5 years prior to registration:\n\n  * Non-small cell lung cancer\n  * Melanoma\n  * Breast cancer\n  * Renal cell carcinoma\n  * Gastrointestinal cancer\n  * If the original histologic proof of malignancy is greater than 5 years, then more recent pathologic confirmation (e.g., from a systemic site or brain metastasis) or unequivocal imaging confirmation of extracranial metastatic disease (e.g. CT of the chest\u002Fabdomen\u002Fpelvis, positron emission tomography \\[PET\\]\u002FCT, etc.) is required\n* Patients must have at least 1 and up to 8 total intact brain metastases detected on a contrast-enhanced MRI performed ≤ 21 days prior to registration\n* At least 1 of the up to 8 lesions must be a study eligible lesion, defined as lesion with a maximum diameter as measured on any orthogonal plane (axial, sagittal, coronal) of ≥ 1.0 cm and ≤ 3.0 cm\n* All brain metastases must be located outside of the brainstem and ≥ 5 mm from the optic nerves or optic chiasm and ≤ 3.0 cm in maximum dimension\n\n  * Note: brainstem metastases per the MRI within 21 days of registration are an exclusion criterion; however, if the MRI used for treatment planning performed within 7 days of SRS\u002FFSRS reveals a brainstem metastasis, the patient remains eligible if the patient is considered an appropriate radiosurgery candidate per the local investigator\n* Patients must have a diagnosis-specific graded prognostic assessment ≥ 1.5\n* No more than 2 lesions planned for resection if clinically indicated\n* No known leptomeningeal disease (LMD)\n\n  * Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and\u002For unequivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion\n* Age ≥ 18 years\n* Karnofsky performance status (KPS) ≥ 60\n* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal\n* No prior radiotherapy to the brain (partial or whole brain irradiation, SRS, FSRS, or prophylactic cranial irradiation \\[PCI\\])\n* New York Heart Association Functional Classification II or better (NYHA Functional Classification III\u002FIV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)\n* No active infection currently requiring intravenous (IV) antibiotic management\n* No hepatic insufficiency resulting in clinical jaundice and\u002For coagulation defects\n* No chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy",{"count":51,"type":20},269,[23],"This phase III trial compares the effectiveness of fractionated stereotactic radiosurgery (FSRS) to usual care stereotactic radiosurgery (SRS) in treating patients with cancer that has spread from where it first started to the brain. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. FSRS delivers a high dose of radiation to the tumor over 3 treatments. SRS is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. FSRS may be more effective compared to SRS in treating patients with cancer that has spread to the brain.",[26,27,55,28,56,57,58,59,30,60],"Metastatic Digestive System Carcinoma","Metastatic Malignant Neoplasm in the Brain","Metastatic Malignant Solid Neoplasm","Metastatic Melanoma","Metastatic Renal Cell Carcinoma","Stage IV Renal Cell Cancer AJCC v8",{"date":34,"type":35},{"date":63,"type":35},"2024-12-12",{"date":65,"type":20},"2028-06-30",{"name":41,"class":42},270,{"id":69,"slug":4,"hasResults":11,"nctId":70,"briefTitle":71,"officialTitle":72,"acronym":4,"eligibilityCriteria":73,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":74,"targetDuration":4,"studyType":21,"phases":76,"briefSummary":79,"conditions":80,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":83,"lastUpdatePostDateStruct":84,"startDateStruct":86,"completionDateStruct":88,"leadSponsor":90,"locationsCount":93},"100593868","NCT07012031","Sotorasib in Combination With Trastuzumab Deruxtecan for the Treatment of Locally Advanced and Metastatic Non-small Cell Lung Cancer With a KRAS G12C Mutation","A Phase I\u002FII Study Evaluating the Safety, Tolerability, and Efficacy of Sotorasib Plus Trastuzumab Deruxtecan in Patients With Advanced Non-Small Cell Lung Cancer With a KRASG12C Mutation","Inclusion Criteria:\n\n* Patients must have histologically or cytologically documented locally advanced or metastatic KRAS\\^G12C-mutant NSCLC that has previously been treated with a KRAS\\^G12C inhibitor AND an immune checkpoint inhibitor (ICI) AND chemotherapy, either given concurrently or sequentially, UNLESS they have any contra-indications to any drug class described above\n* Patients must have KRAS\\^G12C mutation identified by tumor tissue or plasma circulating tumor deoxyribonucleic acid (ctDNA) profiling using a Clinical Laboratory Improvement Act (CLIA) certified College of American Pathologists (CAP) accredited platform; local molecular testing will be allowed. Testing must have been done within the last 5 years before enrollment in this study\n* Data must be available for which prior KRAS\\^G12C inhibitor treatment the patient has received and the dates that they received it (type of KRAS\\^G12C inhibitor used and start and end dates must be collected prior to enrollment)\n* Data must be available on the date patients received the last dose of KRAS\\^G12C inhibitor and the date of disease progression on their last treatment prior to screening for this trial. Data must be available on the last treatment they received and if it was not or did not include a KRAS\\^G12C inhibitor. The time between last KRAS\\^G12C inhibitor and treatment on this trial will be collected prior to enrollment\n* Data must be available on historical HER2 immunohistochemistry (IHC) status (date of test, type of antibody used for the IHC test, scoring system \\[i.e., breast versus (vs.) gastric\\], and results must be collected prior to enrollment). Patients must also have ERBB2 (HER2) mutations status identified by tumor tissue or plasma ctDNA profiling; local (i.e., commercial or institutional next generation sequencing \\[NGS\\]) molecular testing will be allowed. Patients who do not have this information available for collection will not be enrolled on this study\n* Patients must have measurable disease, as defined by RECIST v1.1 using computed tomography (CT) or magnetic resonance imaging (MRI). Previously irradiated lesions cannot be counted as target lesions unless there has been demonstrated progression in the lesions since radiotherapy and no other lesions are available for selection as target lesions\n* Age ≥ 18 years at date of informed consent form signature\n\n  * Because no dosing or adverse event data are currently available on the use of sotorasib (AMG-510) in combination with trastuzumab deruxtecan (DS-8201a) in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)\n* Hemoglobin ≥ 9 g\u002FdL (within 14 days of enrollment)\n* Leukocytes ≥ 3,000\u002FmcL (within 14 days of enrollment)\n* Absolute neutrophil count ≥ 1,500\u002FmcL (within 14 days of enrollment)\n\n  * No administration of granulocyte colony stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment\n* Platelets ≥ 100,000\u002FmcL (within 14 days of enrollment)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (within 14 days of enrollment), (\\\u003C 3 x ULN in the presence of documented Gilbert's syndrome or liver metastases at baseline)\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 x institutional ULN (within 14 days of enrollment) (\\\u003C 5 x ULN in participants with liver metastases)\n* Serum albumin ≥ 2.5 g\u002FdL (within 14 days of enrollment)\n* International normalized ratio (INR)\u002Fprothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (within 14 days of enrollment)\n* Creatinine ≤ 1.5 x institutional ULN OR creatinine clearance (CrCL) ≥ 30 mL\u002Fmin\u002F as determined by (using actual body weight) (within 14 days of enrollment)\n* Patients must have left ventricular ejection fraction (LVEF) ≥ 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before enrollment\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible with 1 day washout for stereotactic radiosurgery (SRS) and 2 weeks washout for whole brain radiation (WBRT)\n* Patients with new or progressive brain metastases (active brain metastases) are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required during the first cycle of therapy\n* Patients must have a life expectancy of ≥ 12 weeks\n* Patients must have a corrected QT interval (QTc) ≤ 470 msec for women and ≤ 450 msec for men (based on average screening triplicates)\n* Patients must be willing to undergo a mandatory pre-treatment biopsy (28 days before treatment starts on cycle 1 day 1 \\[C1D1\\]) for patients enrolled into the expansion phase (phase II). The pre-treatment biopsy is optional for patients enrolled into the dose escalation phase (phase I)\n* Patients must have the ability to ingest and retain oral (PO) medications\n* The effects of the combination of sotorasib (AMG-510) and trastuzumab deruxtecan (DS-8201a) on the developing human fetus are unknown. For this reason and because HER-2-directed antibody conjugated to a topoisomerase 1 inhibitor agents are known to be teratogenic, women of child-bearing potential (WOCBP) must agree to use dual methods of contraception and must have a negative serum pregnancy testing at screening. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women treated or enrolled on this protocol must agree to use a highly effective method of contraception, if sexually active, or avoid intercourse during the study treatment and for 7 months following the last dose of study drug. Sotorasib (AMG-510) may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method on study and for an additional 7 days after the last dose of sotorasib (AMG-510). Men treated or enrolled on this protocol must also agree to use a highly effective barrier method of contraception, if sexually active, or avoid intercourse throughout the duration of the study and for 4 months following the last dose of study drug. To prevent exposure of the unborn child to sotorasib (AMG-510) through semen, male subjects will be required to practice true sexual abstinence (not have sex) or must wear a condom during vaginal sex\n* Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \\[FSH\\] \\> 40 mIU\u002FmL and estradiol \\\u003C 40 pg\u002FmL \\[\\\u003C 147 pmol\u002FL\\] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method\n* Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in this study\n* Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants\n\nExclusion Criteria:\n\n* Patients with a history of (non-infectious) interstitial lung disease (ILD) that required steroids, has current ILD, or where suspected ILD cannot be ruled out by imaging at screening. These patients will be excluded because trastuzumab deruxtecan (DS-8201a) is known to increase the risk of developing ILD and pneumonitis\n* Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \\[COPD\\], restrictive lung disease, prior complete pneumonectomy), and any autoimmune, connective tissue or inflammatory disorders (e.g., rheumatoid arthritis, Sjogren's, sarcoidosis, etc.) where there is documented or a suspicion of pulmonary involvement or pneumonectomy at the time of screening. These patients will be excluded because trastuzumab deruxtecan (DS-8201a) is known to increase the risk of developing ILD and pneumonitis\n* Patients who have had chest radiation therapy within 4 weeks (2 weeks for palliative stereotactic body radiation therapy). These patients will be excluded because trastuzumab deruxtecan (DS-8201a) and sotorasib (AMG-510) are known to increase the risk of developing pneumonitis\n* Patients who have had a major surgery and are not yet fully healed from surgical incisions\n* Patients who have had prior treatment with an antibody drug conjugate with a topoisomerase 1 inhibitor payload (i.e., sacituzumab govitecan, datopotomab deruxtecan, or trastuzumab deruxtecan) or with a topoisomerase inhibitor\n* Patients with a history of significant lung disease requiring systemic corticosteroids treatment (\\> 10 mg of prednisone daily) within the last six months of registration\n* Based on pre-clinical data, trastuzumab deruxtecan (DS-8201a) is associated with corneal disease. Patients with clinically significant corneal disease, in the opinion of the investigator, will be excluded from this study\n* Patients with spinal cord compression, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms\n* Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia. Subjects with chronic grade 2 toxicities (i.e., defined as no worsening to \\> grade 2 for at least 3 months prior to first exposure to study intervention and managed with standard of care treatment) may be eligible per the discretion of the investigator after consultation with the sponsor medical monitor or designee (e.g., grade 2 chemotherapy-induced neuropathy). Subjects should no longer be symptomatic nor require treatment with corticosteroids (prednisone \\> 10 mg or equivalent) or anticonvulsants and must have recovered from the acute toxic effect of radiotherapy\n* Patients who are receiving any other investigational agents\n* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to sotorasib (AMG-510), such as adagrasib, or trastuzumab deruxtecan (DS-8201a)\n* Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies\n* Patients who are taking strong CYP3A4 inducers should be switched to an alternative drug\n* Avoid coadministration with P-glycoprotein (P-gp) substrates for which minimal concentration changes may lead to serious toxicities. If coadministration cannot be avoided, dose adjustment of the substrate may be required. Please refer to the prescribing information for the substrate\n* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous or interfere with the evaluation of the clinical study results\n* Pregnant women are excluded from this study because trastuzumab deruxtecan (DS-8201a) is a HER2-directed antibody conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with trastuzumab deruxtecan (DS-8201a) breastfeeding should be discontinued if the mother is treated with trastuzumab deruxtecan (DS-8201a). These potential risks may also apply to other agents used in this study\n* Patients with uncontrolled or significant cardiovascular disease (i.e., history of myocardial infarction within 6 months from screening, symptomatic congestive heart failure \\[CHF\\] \\[New York Heart Association class II to IV\\], troponin levels consistent with myocardial infarction 28 days prior to enrollment, history of unstable angina, or serious cardiac arrhythmia)\n* Patients with prior history of pneumonitis grade 2 or higher or ILD\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients unable to receive both iodinated contrast for CT scans and gadolinium contrast for MRI scans\n* Patients that have pleural effusion, ascites, or pericardial effusion that requires drainage within 2 weeks of study screening procedures, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART)\n* Patients that have received a live vaccine within 30 days prior to the first dose of study drug will be excluded. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella\u002Fzoster (chicken pox), yellow fever, rabies, bacillus Calmette- Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed",{"count":75,"type":20},37,[77,78],"PHASE1","PHASE2","This phase I\u002FII trial tests the safety, side effects and best dose of sotorasib with trastuzumab deruxtecan and how well the combination works in treating patients with KRAS G12C mutated non-small cell lung cancer that has spread to nearby tissues or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Sotorasib blocks a protein made by the mutated KRAS gene (KRAS p.G12C), which may help keep tumor cells from growing and may kill them. It is a type of targeted therapy. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Giving sotorasib in combination with trastuzumab deruxtecan may be safe, tolerable, and\u002For effective in treating patients with locally advanced or metastatic non-small cell lung cancer with a KRAS G12C mutation.",[81,28,82,30],"Locally Advanced Lung Non-Small Cell Carcinoma","Stage III Lung Cancer AJCC v8","2026-06-19",{"date":85,"type":35},"2026-06-23",{"date":87,"type":35},"2026-06-17",{"date":89,"type":20},"2027-06-14",{"name":91,"class":92},"National Cancer Institute (NCI)","NIH",9,{"id":95,"slug":4,"hasResults":11,"nctId":96,"briefTitle":97,"officialTitle":98,"acronym":4,"eligibilityCriteria":99,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":100,"targetDuration":4,"studyType":21,"phases":102,"briefSummary":103,"conditions":104,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":106,"lastUpdatePostDateStruct":107,"startDateStruct":108,"completionDateStruct":110,"leadSponsor":112,"locationsCount":114},"100594314","NCT07017829","GT103 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic STK11 Mutant Non-Small Cell Lung Cancer","A Phase II Trial of GT103 in Combination With Pembrolizumab in STK11 Mutant Non-Small Cell Lung Cancer (NSCLC)","Inclusion Criteria:\n\n* Age ≥ 18 years.\n* Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at the time of study treatment initiation.\n* Have pathologically confirmed diagnosis of STK11 mutant NSCLC. STK11 mutation will be based on subject's local clinically accredited laboratory testing (Clinical Laboratory Improvement Amendments \\[CLIA\\]-certified) using deoxyribonucleic acid (DNA) sequencing test.\n* Must have progressed on a pembrolizumab containing regimen and eligible for continuing pembrolizumab post-progression as determined by treating physician. Other anti-PD-1 or anti-PD-L1 checkpoint inhibitors may also be used in place of pembrolizumab\n\n  \\_Adequate bone marrow and organ function as defined by the following lab values:\n* Absolute neutrophil count (ANC) ≥ 1.5 x 10\\^9\u002FL.\n* Platelets ≥ 100 x 10\\^9\u002FL.\n* Hemoglobin ≥ 9 g\u002FdL.\n* Estimated glomerular filtration rate (GFR) (measured or calculated with Cockroft and Gault formula) \\> 45mL\u002Fmin.\n* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) (ALT and AST ≤ 5 x ULN is acceptable if liver metastases are present).\n* Total bilirubin ≤ 1.5 x ULN. For patients with well documented Gilbert's syndrome, total bilirubin ≤ 3 x ULN with direct bilirubin within normal range.\n* Troponin-I ≤ ULN and B-type natriuretic peptide test (BNP) \\\u003C 200 pg\u002FmL.\n* Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) (institutional limit).\n* Patients must have measurable disease as defined in Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.\n* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.\n* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee\u002FInstitutional Review Board approved written informed consent form prior to receiving any study related procedure.\n* Participant agrees to provide blood samples at the start of treatment and at multiple times during the study. Participant agrees to provide tumor biopsy tissue or have adequate archival formalin-fixed paraffin-embedded (FFPE) tissue available.\n\nExclusion Criteria:\n\n* Receipt of anticancer chemotherapy within 4 weeks before the first administration of study drug.\n* Prior radiotherapy or gamma knife within 2 weeks of study treatment for non-brain metastasis. Subjects must have recovered from all radiation related toxicities.\n* Active\u002Funtreated brain metastasis. Whole brain radiation or gamma knife radiosurgery performed less than 4 weeks prior to first administration of study drug. Previously treated brain metastasis allowed as long as not requiring steroids and stable on imaging at least 4 weeks after completing radiation therapy.\n* Leptomeningeal involvement regardless of treatment status.\n* Tumor with oncogenic mutation based on standard of care broad genomic profiling in EGFR, ALK, ROS1, RET, MET, or NTRK genes.\n* History of autoimmune disorder, with exception of patients with vitiligo or endocrine-related autoimmune conditions receiving appropriate hormonal supplementation who are eligible. Systemic use of immunosuppressant drugs such as steroids (except as hormone replacement therapy or short-course supportive medication such as chemotherapy or drug allergy, etc.), azathioprine, tacrolimus, cyclosporine, etc. within 4 weeks before the first administration of study drug.\n* Currently receiving or has received systemic corticosteroids within 4 weeks prior to starting study drug for management of brain metastases, or who have not fully recovered from side effects of such treatment. Steroids for endocrine replacement or receipt of short-course of steroids during the preceding 4 week period as supportive medication such as for drug allergy, anti-emetic, etc. is allowed.\n* Had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery.\n* Has known immunosuppressive disease (e.g., HIV, AIDS or other immune depressing disease). Testing is not mandatory.\n* Active, clinically serious infections or other serious uncontrolled medical conditions.\n* Patient has known hypersensitivity to the components of the study drugs or any analogs.\n* History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:\n\n  * Myocardial infarction or arterial thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease.\n  * History of documented congestive heart failure (New York Heart Association functional classification III or IV) within 6 months prior to baseline.\n  * Uncontrolled hypertension (systolic blood pressure \\[SBP\\] \\> 160\u002Fdiastolic blood pressure \\[DBP\\] \\> 100 despite medical intervention).\n  * History of myocarditis of any etiology.\n  * History of ventricular arrhythmias.\n* Patients diagnosed with an invasive cancer within 2 years prior to starting protocol therapy with the following exceptions: non-melanoma skin cancers, in-situ cancers, and prostate cancer Gleason ≤ 6 (under surveillance or treated), early-stage node-negative estrogen receptor positive (ER+)\u002Fprogesterone receptor positive (PR+) breast cancer with Oncotype Dx score \\\u003C 25 not taking adjuvant hormonal therapy.\n* Pregnant or nursing female participants.\n* Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug.\n* Unwilling or unable to follow protocol requirements.",{"count":101,"type":20},28,[78],"This phase II trial tests how well GT103 in combination with pembrolizumab works in treating patients with STK11 mutant non-small cell lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). GT103 is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. GT103 targets the tumor cell-protein complement factor H found on some cancer cells and may provide specific anti-tumor activity that may help block the formation of growths that may become cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving GT103 in combination with pembrolizumab may kill more cancer cells and improve outcomes in patients with advanced or metastatic STK11 mutant non-small cell lung cancer.",[105,28,82,30],"Advanced Lung Non-Small Cell Carcinoma","2026-06-18",{"date":32,"type":35},{"date":109,"type":35},"2026-04-01",{"date":111,"type":20},"2028-12-01",{"name":113,"class":42},"Roswell Park Cancer Institute",1,{"id":116,"slug":4,"hasResults":11,"nctId":117,"briefTitle":118,"officialTitle":119,"acronym":4,"eligibilityCriteria":120,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":121,"targetDuration":4,"studyType":21,"phases":123,"briefSummary":124,"conditions":125,"keywords":4,"overallStatus":130,"whyStopped":4,"lastUpdateSubmitDate":106,"lastUpdatePostDateStruct":131,"startDateStruct":132,"completionDateStruct":134,"leadSponsor":136,"locationsCount":114},"100588612","NCT06943664","Photoimmunotherapy With ASP-1929 and Cemiplimab for the Treatment of Refractory, Inoperable, and Metastatic Stage IIIB-IV Non-small Cell Lung Cancer","Phase II Trial: Photoimmunotherapy and Anti-PD1 in Patients With Refractory Inoperable and Metastatic Non-Small Cell Lung Cancer","Inclusion Criteria:\n\n* Age ≥ 18 years of age\n* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2\n* Subjects with histologically or cytologically confirmed stage IIIB-IV NSCLC\n* Subjects lacking actionable genetic mutations must have been previously treated with (a) anti-PD-1\u002FPD-L1 therapy; and (b) platinum-based chemotherapy, either as combination or sequentially for metastatic disease and have progressed on or after therapy. Individuals who cannot tolerate or have previously refused platinum-based chemotherapy or who are unable to receive it are eligible to enroll based on progression after anti-PD-1\u002FPD-L1 therapy alone\n* NSCLC with known actionable genomic alteration (e.g., EGFR, ALK, ROS1, BRAF) must have received all approved targeted therapies and have progressed (data capture not necessary for ALK, ROS1, BRAF)\n* Subjects have at least two lesions of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n* At least one site of disease accessible to photoimmunotherapy. Thus, the therapeutic 690-nm laser light can be administered via insertion of optical fiber\u002Fs in the target tumor for interstitial photoimmunotherapy (I-PIT), or target tumors can be illuminated with external beam photoimmunotherapy (EB-PIT)\n* Absolute neutrophil count: ≥ 1,000\u002FµL\n* Platelets: ≥ 100,000\u002FµL\n* Total bilirubin: ≤ institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \\[SGPT\\]): ≤ 3 x institutional ULN\n* Creatinine clearance (CrCl) ≥ 50 mL\u002Fmin (Cockcroft-Gault)\n* Patient has not received a transfusion within 2 weeks prior to screening\n* Female patients of childbearing potential must have a negative pregnancy test at screening and must be willing to use 2 methods of highly effective birth control while on study or be surgically sterile, or abstain from heterosexual sexual activity for the course of the study through 120 days after the last dose of anti-PD1 treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately\n* Male participants must agree to use a highly effective method of contraception starting with the first dose of study medication through 120 days after the last dose of anti-PD1 treatment\n* Participant must understand the investigational nature of this study and sign an independent ethics committee\u002Finstitutional review board approved written informed consent form prior to receiving any study related procedures\n\nExclusion Criteria:\n\n* Has received an investigational agent within 30 days prior to initial treatment or less than 4 half-lives of a previous drug\n* Had a major surgery, (e.g., requiring general anesthesia) within 4 weeks before the first dose of study treatment or, will not have fully recovered from surgery prior to the first dose\n* Patients who received chemotherapy or chemoimmunotherapy within 21 days or those who have not recovered from reversible adverse events prior to the scheduled surgery and interstitial or intraoperative PIT\n* The participants received high dose or curative radiotherapy to the target tumor\u002Fs within 30 days prior to the planned I-PIT or EB-PIT\n* Toxicity related to prior anticancer therapy that has not returned to grade ≤ 1 or baseline levels (except for alopecia, vitiligo, grade ≤ 2 peripheral neuropathy, and endocrinopathies that are stable on hormone replacement, which may be grade 2)\n* History of immune-related adverse events (irAEs) from prior anticancer therapy leading to permanent treatment discontinuation\n* History of solid organ or hematologic stem cell transplantation\n* Prolonged corrected QT interval by Fredericia (QTcF) \\> 470 msec or clinically significant cardiac arrhythmia or electrophysiologic disease (e.g., placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate or abnormalities in conduction or morphology of electrocardiogram \\[ECG\\] \\[e.g., complete left bundle branch block, third- or second-degree heart block, PR interval \\> 250 msec\\]). Note: Participants with cardiac pacemakers who are clinically stable are eligible\n* Clinically significant cardiovascular disease, including any of the following within 6 months prior to signature of informed consent:\n\n  * Myocardial infarction, severe or unstable angina, or coronary artery bypass surgery\n  * Clinically significant arrhythmias (e.g., ventricular arrhythmias or atrial fibrillation with uncontrolled heart rate)\n  * Congestive heart failure (New York Heart Association \\[NYHA\\] class III\u002FIV)\n  * Cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event\n  * Myocarditis\n* Active bleeding diathesis or requirement for therapeutic anticoagulation that cannot be interrupted or altered for procedures\n* Patients with untreated or symptomatically unstable treated brain metastases or history of leptomeningeal disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with treated and stable brain metastases (at least 28 days from last radiotherapy treatment) are eligible as long as steroids are not required for symptom management\n* Known history of hepatitis B, hepatitis C or human immunodeficiency virus (HIV). Exceptions include past or resolved hepatitis B (defined as the presence of hepatitis B core antibody \\[anti-HBc\\] and absence of hepatitis B virus surface antigen \\[HBsAg\\]) and patients positive for hepatitis C (hepatitis C virus \\[HCV\\]) antibody if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). HIV testing is not required in absence of clinical suspicion of HIV\n* History of, or active autoimmune disorder, requiring systemic steroids or immunosuppressive agents. Exceptions allowed: Patients with autoimmune dermatologic conditions not requiring systemic steroids or immunosuppressive agents (e.g. vitiligo, eczema, etc.), endocrine-related autoimmune conditions receiving appropriate hormonal supplementation\n\n  * Use of immunosuppressant drugs such as steroids, azathioprine, tacrolimus, cyclosporine, etc. is not permitted within 4 weeks before recruitment (exception allowed is use of steroids as hormone replacement therapy or as supportive medication e.g. anti-emesis, contrast allergy, pre-medication, etc. or other short-course therapy less than 2 weeks continuously within 4 weeks of study treatment)\n* History of significant (≥ grade 3) cetuximab infusion reactions\n* Evidence of interstitial lung disease or current active, noninfectious pneumonitis\n* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \\[e.g. colitis or Crohn's disease\\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \\[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\\]). The following are exceptions to this criterion:\n\n  * Patients with vitiligo or alopecia\n  * Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement\n  * Any chronic skin condition that does not require systemic therapy\n  * Patients without active disease in the last 5 years may be included\n  * Patients with celiac disease controlled by diet alone\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive ASP-1929\n* Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive the experimental PIT or immunotherapy\n* Pregnant or nursing female participants\n* Unwilling or unable to follow protocol requirements",{"count":122,"type":20},27,[78],"This phase II trial tests how well photoimmunotherapy (PIT) with ASP-1929 in combination with cemiplimab works in treating patients with stage IIIB-IV non-small cell lung cancer (NSCLC) that has not responded to previous treatment (refractory), that is not suitable for surgery (inoperable), or that has spread from where it first started to other places in the body (metastatic). PIT is a treatment that combines drugs that become active when exposed to light, such as ASP-1929, with immunotherapy to target and kill tumor cells. ASP-1929 combines cetuximab with a light-sensitive component, sarotalocan. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called epidermal growth factor receptor (EGFR), which is found on some types of tumor cells. This may help keep tumor cells from growing. Sarotalocan is a fluorescent dye, infrared-activated fluorescent dye 700, that is light sensitive, and when activated by a special type of laser light, helps destroy or change tumor cells. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving PIT with ASP-1929 in combination with cemiplimab may kill more tumor cells in patients with refractory, inoperable, or metastatic stage IIIB-IV NSCLC.",[126,28,127,128,129,30],"Lung Non-Small Cell Carcinoma","Refractory Lung Non-Small Cell Carcinoma","Stage IIIB Lung Cancer AJCC v8","Stage IIIC Lung Cancer AJCC v8","NOT_YET_RECRUITING",{"date":32,"type":35},{"date":133,"type":20},"2026-08-15",{"date":135,"type":20},"2028-05-01",{"name":113,"class":42},{"id":138,"slug":4,"hasResults":11,"nctId":139,"briefTitle":140,"officialTitle":141,"acronym":142,"eligibilityCriteria":143,"healthyVolunteers":11,"sex":16,"minAge":144,"maxAge":4,"enrollmentInfo":145,"targetDuration":4,"studyType":21,"phases":147,"briefSummary":148,"conditions":149,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":106,"lastUpdatePostDateStruct":239,"startDateStruct":240,"completionDateStruct":242,"leadSponsor":244,"locationsCount":114},"100459958","NCT05269381","Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors","A Phase I\u002FII Study of Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab in Advanced Solid Tumors (PNeoVCA)","PNeoVCA","Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.\n\nPHASE I PRE-REGISTRATION, ALL:\n\n* Willing to provide tissue specimens per protocol\n\n  * NOTE: includes fresh tissue specimen at pre-registration for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo Institutional Review Board (IRB) protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration.\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n* Willing to provide blood specimens for research\n* Negative pregnancy test =\\\u003C 7 days prior to pre-registration for persons of childbearing potential. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1\n* Anticipated life expectancy \\> 6 months\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).\n* The following lab values obtained =\\\u003C 28 days prior to pre-registration:\n\n  * Hemoglobin \\>= 9.0 g\u002FdL (Must be \\>= 7 days after most recent transfusion)\n  * Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3 or \\>= 1.5 X 10\\^9\u002FL\n  * Platelet count \\>= 100,000\u002Fmm\\^3 or \\>= 100 X 10\\^9\u002FL (Must be \\>=7 days after most recent transfusion)\n  * Total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN)\n  * Aspartate transaminase (AST) and alanine transaminase (ALT) =\\\u003C 3 x ULN or =\\\u003C 5 x ULN with liver metastases\n  * Creatinine =\\\u003C 1.5 x ULN OR calculated creatinine clearance must be \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n  * International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy\n\nPHASE I REGISTRATION, ALL:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood and tissue specimens for research\n* Willing to return to enrolling institution for follow-up\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have also received and progressed on at least one line of prior FDA-approved targeted therapy\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only\n\n  * NOTE: If urine test cannot be confirmed negative, serum pregnancy test will be required\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (for laboratory toxicity see specified limits for inclusion) or NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nPHASE II PRE-SCREENING COHORT 3 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of adenocarcinoma of the breast with estrogen receptor (ER) \\\u003C 10%, progesterone receptor (PR) \\\u003C 10%, and HER2 negative based on current American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guideline\n* Stage I-III based on 7th edition of TNM staging system from American Joint Committee on Cancer (AJCC)\n* Evidence of residual disease \\>= 1 cm after neoadjuvant pembrolizumab-based chemotherapy on imaging for patients who have not had surgery\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-SCREENING COHORT 4 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of lung NSCLC\n* No actionable EGFR mutations and ALK fusions\n* Stage II or stage III based on AJCC 8th\n* Tumor \\>= 2 cm on pre-surgery evaluation imaging (residual disease \\>= 2 cm after neoadjuvant therapy on pre-surgery evaluation imaging in patient who receives neoadjuvant therapy) for patients who have not had surgery. Patients with or without neoadjuvant chemotherapy or immunotherapy are allowed\n* Provide written informed consent\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-REGISTRATION COHORT 3 (TNBC) ONLY:\n\n* Histologically confirmed residual cancer burden 2 and 3 in surgical specimens\n\nPHASE II PRE-REGISTRATION COHORT 4 (NSCLC) ONLY:\n\n* Tumor without complete pathologic response is confirmed in pathology\n* Willing to proceed with surgery and provide tissue specimens for complete exome and transcriptome sequencing\n\n  * NOTE: Patients who had sequencing under certain Mayo IRB protocols and neoantigens identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration\n* Negative pregnancy test ≤7 days prior to pre-registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* ECOG PS of 0 or 1\n* Anticipated life expectancy \\> 6 months\n\nPHASE II REGISTRATION:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Patients will receive \\>= 2 additional cycles of maintenance pembrolizumab\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood specimens for research\n* Willing to return to enrolling institution for follow-up\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nExclusion Criteria\n\nALL PHASES:\n\n* Any of the following because study involves investigational agent whose genotoxic, mutagenic and teratogenic effects on developing fetus and newborn are unknown:\n\n  * Pregnant person\n  * Nursing person unwilling to stop breast feeding\n  * Person of childbearing potential unwilling to employ adequate contraception from registration through 6 months after final vaccine cycle\n* Co-morbid systemic illnesses or other severe concurrent disease which, in judgment of investigator, would make patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and toxicity of prescribed regimens\n* History of myocardial infarction =\\\u003C 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.\n* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy\n\nPHASE I PRE-REGISTRATION:\n\n* Acute, reversible effect(s) of prior therapy not recovered to baseline regardless of interval since last treatment\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Psychiatric illness\u002Fsocial situations\n  * Congestive heart failure with New York Heart Association (NYHA) class III or IV moderate to severe objective evidence of cardiovascular disease\n  * Stroke =\\\u003C 3 months prior to pre-registration\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Receiving any other investigational agent which would be considered treatment for primary neoplasm, except pembrolizumab\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* History of active autoimmune disease (AD) that required systemic treatment in =\\\u003C 30 days (i.e., use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with celiac disease controlled with diet modification are not excluded PHASE I REGISTRATION\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major Surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n  * Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= Grade 3 treatment-emergent adverse event (TEAE) to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent permitted in absence of active AD\n* Evidence of leptomeningeal disease or central nervous system metastases that are untreated, symptomatic, or require steroids \\>10 mg daily prednisone equivalent\n\n  * NOTE: Patients with history of stable treated brain metastases are eligible. Stable treated metastases defined as no evidence of progression for ≥4 weeks on brain imaging (MRI or CT scan)\n\nPHASE II PRE-SCREENING:\n\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-screening\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-screening\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n\nPHASE II PRE-REGISTRATION\n\n* Uncontrolled illness including, but not limited to:\n\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If history of prior malignancy, must not be receiving other specific treatment for cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n* Patients will also be excluded based on tissue\u002Fribonucleic acid (RNA)\u002Fdeoxyribonucleic acid (DNA) quality and quantity. If any of the following quality and quantity thresholds are not met, patient will be excluded: (1) tumor tissue cellularity equal to or greater than 30%; (2) there are \\>= 2 cores with passing cellularity; (3) \\>= 30% of tumor RNA with fragment sizes are \\>= 200 base pairs (DV200 \\>= 30); (4) \\\u003C 10% of DNA fragments are smaller than 1 kb; and (5) sufficient amount of both DNA (blood and tumor) and RNA (tumor) for exome sequencing and whole transcriptome sequencing (RNAseq) according to Mayo sequencing core. (Kits and technologies change overtime, so these are not fixed numbers.)\n\nPHASE II REGISTRATION\n\n* Evidence of metastatic disease or recurrence\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n\n    * NOTE: Continuation of pembrolizumab per standard of care is allowed\n    * NOTE: Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= grade 3 TEAE to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy), or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Requirement for systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent are permitted in","16 Years",{"count":146,"type":20},132,[77,78],"This phase I\u002FII trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.",[150,151,152,153,26,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,81,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,28,57,58,190,59,191,192,193,194,195,196,82,197,198,199,200,201,202,203,128,204,129,205,206,207,208,209,210,30,60,211,212,213,214,215,216,217,218,219,220,221,222,223,224,225,226,227,228,229,230,231,232,233,234,235,236,237,238],"Anatomic Stage III Breast Cancer AJCC v8","Anatomic Stage IIIA Breast Cancer AJCC v8","Anatomic Stage IIIB Breast Cancer AJCC v8","Anatomic Stage IIIC Breast Cancer AJCC v8","Clinical Stage III Cutaneous Melanoma AJCC v8","Clinical Stage III Gastric Cancer AJCC v8","Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage III Merkel Cell Carcinoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Clinical Stage IV Gastric Cancer AJCC v8","Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IV Merkel Cell Carcinoma AJCC v8","Clinical Stage IVA Gastric Cancer AJCC v8","Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IVB Gastric Cancer AJCC v8","Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Locally Advanced Cervical Carcinoma","Locally Advanced Endometrial Carcinoma","Locally Advanced Gastric Adenocarcinoma","Locally Advanced Gastroesophageal Junction Adenocarcinoma","Locally Advanced Head and Neck Squamous Cell Carcinoma","Locally Advanced Hepatocellular Carcinoma","Locally Advanced Malignant Solid Neoplasm","Locally Advanced Melanoma","Locally Advanced Merkel Cell Carcinoma","Locally Advanced Renal Cell Carcinoma","Locally Advanced Skin Squamous Cell Carcinoma","Locally Advanced Triple-Negative Breast Carcinoma","Locally Advanced Unresectable Breast Carcinoma","Locally Advanced Unresectable Cervical Carcinoma","Locally Advanced Unresectable Gastric Adenocarcinoma","Locally Advanced Unresectable Gastroesophageal Junction Adenocarcinoma","Locally Advanced Unresectable Renal Cell Carcinoma","Locally Advanced Urothelial Carcinoma","Metastatic Cervical Carcinoma","Metastatic Endometrial Carcinoma","Metastatic Gastric Adenocarcinoma","Metastatic Gastroesophageal Junction Adenocarcinoma","Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hepatocellular Carcinoma","Metastatic Merkel Cell Carcinoma","Metastatic Skin Squamous Cell Carcinoma","Metastatic Triple-Negative Breast Carcinoma","Metastatic Urothelial Carcinoma","Skin Squamous Cell Carcinoma","Stage III Cervical Cancer AJCC v8","Stage III Hepatocellular Carcinoma AJCC v8","Stage III Renal Cell Cancer AJCC v8","Stage IIIA Cervical Cancer AJCC v8","Stage IIIA Hepatocellular Carcinoma AJCC v8","Stage IIIA Lung Cancer AJCC v8","Stage IIIA Uterine Corpus Cancer AJCC v8","Stage IIIB Cervical Cancer AJCC v8","Stage IIIB Hepatocellular Carcinoma AJCC v8","Stage IIIB Uterine Corpus Cancer AJCC v8","Stage IIIC Uterine Corpus Cancer AJCC v8","Stage IIIC1 Uterine Corpus Cancer AJCC v8","Stage IIIC2 Uterine Corpus Cancer AJCC v8","Stage IV Cervical Cancer AJCC v8","Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IVA Cervical Cancer AJCC v8","Stage IVA Hepatocellular Carcinoma AJCC v8","Stage IVA Lung Cancer AJCC v8","Stage IVA Uterine Corpus Cancer AJCC v8","Stage IVB Cervical Cancer AJCC v8","Stage IVB Hepatocellular Carcinoma AJCC v8","Stage IVB Lung Cancer AJCC v8","Stage IVB Uterine Corpus Cancer AJCC v8","Triple-Negative Breast Carcinoma","Unresectable Cervical Carcinoma","Unresectable Endometrial Carcinoma","Unresectable Gastric Adenocarcinoma","Unresectable Gastroesophageal Junction Adenocarcinoma","Unresectable Head and Neck Squamous Cell Carcinoma","Unresectable Hepatocellular Carcinoma","Unresectable Lung Non-Small Cell Carcinoma","Unresectable Malignant Solid Neoplasm","Unresectable Melanoma","Unresectable Merkel Cell Carcinoma","Unresectable Renal Cell Carcinoma","Unresectable Skin Squamous Cell Carcinoma","Unresectable Triple-Negative Breast Carcinoma","Unresectable Urothelial Carcinoma","Breast Adenocarcinoma","Stage III Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8",{"date":85,"type":35},{"date":241,"type":35},"2022-03-31",{"date":243,"type":20},"2028-03-31",{"name":245,"class":42},"Mayo Clinic",{"id":247,"slug":4,"hasResults":11,"nctId":248,"briefTitle":249,"officialTitle":250,"acronym":4,"eligibilityCriteria":251,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":252,"targetDuration":4,"studyType":21,"phases":254,"briefSummary":255,"conditions":256,"keywords":288,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":308,"lastUpdatePostDateStruct":309,"startDateStruct":310,"completionDateStruct":312,"leadSponsor":314,"locationsCount":122},"100499720","NCT05786924","Phase 1\u002F2 Trial of S241656 in Selected RAS\u002FMAPK Mutation- Positive Malignancies","A Phase 1\u002F2, Open-label Study of Oral S241656 (BDTX-4933) as Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With KRAS, BRAF and Other Selected RAS\u002FMAPK Mutation-Positive Malignancies","Key Inclusion Criteria:\n\n* Life expectancy of ≥ 12 weeks in the opinion of the investigator.\n* Histologically or cytologically confirmed recurrent locally advanced (unresectable) or metastatic solid tumors with documented RAS or RAF mutations or alterations.\n* Adequate bone marrow and organ function.\n* Recovered from toxicity to prior anti-cancer therapy.\n\nPart 1 Dose Escalation cohort ONLY:\n\n* Part 1A: Advanced\u002Fmetastatic NSCLC with KRAS non-G12C, HRAS, NRAS, BRAF or CRAF (RAF1) mutations or alterations\n* Part 1B: Advanced\u002Fmetastatic GI tumors (e.g., PDAC, CRC, and BTC) with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations or alterations\n* Part 1C: Advanced\u002Fmetastatic PDAC with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations or alterations\n* Part 1D: Colorectal adenocarcinoma with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations or alterations\n* Part 1E: Other advanced\u002Fmetastatic non-GI, non-NSCLC solid tumors with KRAS, HRAS, NRAS, BRAF, CRAF (RAF1) mutations or alterations\n\nPart 2 Dose Optimization and Expansion cohorts ONLY:\n\n* Part 2A: Advanced\u002Fmetastatic NSCLC with KRAS non-G12C mutations and\u002For BRAF mutations\n* Part 2A1: Advanced\u002Fmetastatic NSCLC with KRAS non-G12C mutations\n* Part 2A2: Advanced\u002Fmetastatic NSCLC with BRAF mutations\n* Part 2A3: Advanced\u002Fmetastatic NSCLC with KRAS non-G12C or BRAF mutations or alterations and active CNS metastatic disease\n* Part 2A4: Advanced\u002Fmetastatic NSCLC with a KRAS G12C mutation\n* Part 2B1: Advanced\u002Fmetastatic PDAC with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations or alterations\n* Part 2B2: Advanced\u002Fmetastatic CRC with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations or alterations\n* Part 2B3: Advanced\u002Fmetastatic BTC (adenocarcinoma) with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations or alterations\n\nKey Exclusion Criteria:\n\n* Cancer that has a known MEK1\u002F2 mutation.\n* Known allergy\u002Fhypersensitivity to excipients of S241656 or to any of the registered IMPs administered in combination.\n* Any contra-indication, to use of any of the combination chemotherapy or anti-EGFR therapy partners administered as part of this trial.\n* Major surgery within 4 weeks of study entry or planned during study.\n* Ongoing anticancer therapy.\n* Ongoing radiation therapy.\n* Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy.\n* Clinically significant cardiovascular disease.\n* Symptomatic spinal cord compression.\n* Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years.\n* History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.\n* Females who are pregnant or breastfeeding.\n* Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.\n* Prior use of experimental agents that target the KRAS\u002FBRAF\u002FMEK\u002FERK pathway.",{"count":253,"type":20},554,[77,78],"BDTX-4933-101 is a first-in-human, open-label, Phase 1\u002F2 dose escalation, dose optimization and expansion study designed to evaluate the safety and tolerability of S241656 as monotherapy and in combination with other anti-cancer therapies in participants with selected advanced malignancies. The study population for the Dose Escalation part of the study comprises adults with recurrent advanced\u002Fmetastatic non-small cell lung cancer (NSCLC), Gastrointestinal (GI) cancers, and other solid tumors harboring KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (Rapidly Accelerated Fibrosarcoma (RAF1)) mutations or alterations. A dose optimization part in adults with NSCLC may follow the dose escalation phase if the sponsor, in consultation with the safety review committee, decides it is necessary to further characterize the optimal dose. However, the study may also proceed directly to the expansion phase. The study population for the Dose Expansion part of the study comprises adults with advanced\u002Fmetastatic NSCLC with KRAS and\u002For BRAF mutations, and with Pancreatic Ductal AdenoCarcinoma (PDAC), ColoRectal Cancer (CRC), and Biliary Tract Cancer (BTC) with KRAS, HRAS, NRAS, BRAF, and\u002For CRAF (RAF1) mutations and alterations. All patients will self-administer S241656 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study.",[257,258,259,260,261,262,263,264,28,265,266,267,268,269,270,271,272,273,274,275,276,277,278,279,280,281,282,283,284,285,286,287],"Non-small Cell Lung Cancer","Histiocytic Neoplasm","Histiocytosis","BRAF Gene Mutation","BRAF V600E","BRAF V600 Mutation","BRAF Mutation-Related Tumors","BRAF","Metastatic Lung Cancer","Recurrent Lung Cancer","Recurrent Lung Non-Small Cell Carcinoma","NSCLC","Solid Tumor","Solid Carcinoma","KRAS G12D","KRAS G12V","KRAS Mutation-Related Tumors","NRAS Gene Mutation","Thyroid Cancer","Thyroid Carcinoma","Colorectal Cancer","Colorectal Carcinoma","Recurrent Histiocytic and Dendritic Cell Neoplasm","Brain Metastases","Recurrent NSCLC","KRAS G13C","Acquired Resistance to KRAS G12C Inhibitor","KRAS G12A","KRAS G12F","KRAS G12R","KRAS G13D",[289,290,291,292,293,294,295,296,297,298,299,300,301,302,303,304,305,306,307],"BRAF Class I","BRAF Class II","BRAF Class III","KRAS","Intolerant histiocytic neoplasm","BDTX-4933","Phase 1","dose escalation","dose expansion","MAPK","mitogen-activated protein kinase","RAS","RAF","Upstream oncogenic alterations","RAF inhibitor","intracranial disease","CRAF","NRAS","RAF fusions","2026-06-16",{"date":87,"type":35},{"date":311,"type":35},"2023-04-18",{"date":313,"type":20},"2028-06",{"name":315,"class":42},"Institut de Recherches Internationales Servier",{"id":317,"slug":4,"hasResults":11,"nctId":318,"briefTitle":319,"officialTitle":320,"acronym":4,"eligibilityCriteria":321,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":322,"targetDuration":4,"studyType":21,"phases":324,"briefSummary":325,"conditions":326,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":327,"lastUpdatePostDateStruct":328,"startDateStruct":329,"completionDateStruct":331,"leadSponsor":333,"locationsCount":335},"100555897","NCT06518057","Hippocampal Avoidance in Craniospinal Irradiation for the Treatment of Leptomeningeal Metastases From Breast Cancer or Non-small Cell Lung Cancer","A Multi-Center Phase 2 Study of Hippocampal Avoidance in Craniospinal Irradiation for Leptomeningeal Metastases From Solid Tumors","Inclusion Criteria:\n\n* Patients with breast cancer or NSCLC malignancies with leptomeningeal metastases established radiographically and\u002For through CSF cytology\n* Patients who are candidates for radiation therapy for the treatment of leptomeningeal metastases\n* Patients ≥ 18 years old\n* Karnofsky performance status (KPS) ≥ 60 or Eastern Cooperative Oncology Group (ECOG) ≥ 2\n* The patient is able to provide informed consent\n* Hemoglobin \\> 8 g\u002FdL\n* Absolute neutrophil count \\> 1,000\u002Fmm\n* Platelet count \\> 100,000\u002Fmm\n* Participants born female at birth must either be of non-reproductive potential (i.e. post-menopausal by history \\[≥ 60 years old, or with no menses for \\> 1 year without an alternative medical cause\\], OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum \u002Furine pregnancy test within 3 weeks prior to starting radiation therapy (RT)\n* Patients with reproductive potential must agree to practice two highly effective contraceptive methods\n\nExclusion Criteria:\n\n* Patients with multiple, serious major neurologic deficits per physician\u002Finvestigator assessment including encephalopathy\n* Patients with extensive systemic disease and without reasonable systemic treatment options\n* Patients who are unable to undergo MRI brain and spine with gadolinium contrast\n* Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances\n* Gross ventricular disease\n* Brain metastases within 5 mm of the hippocampal contours not previously treated\n* Pregnant or lactating women",{"count":323,"type":20},22,[78],"This phase II clinical trial studies how well craniospinal irradiation (CSI) with hippocampal avoidance, using proton therapy or volumetric modulated arc therapy (VMAT), works in treating patients with breast cancer or non-small cell lung cancer (NSCLC) that has spread from the original (primary) tumor to the cerebrospinal fluid (CSF) and meninges (thin layers of tissue that cover and protect the brain and spinal cord) (leptomeningeal metastases). Radiation therapy is an effective treatment in relieving localized symptoms caused by leptomeningeal metastases. However, the type of radiation therapy typically used does not prevent the spread of leptomeningeal disease. CSI (radiation therapy directed at the brain and spinal cord to kill tumor cells) may be able to target all of the areas of possible leptomeningeal tumor spread. CSI may however result in significant neurological side effects due to radiation damage to a part of the brain called the hippocampus. Hippocampal avoidance (HA) reduces the amount of radiation to the hippocampus. Proton or VMAT CSI with HA may be an effective treatment while reducing neurological side effects for patients with leptomeningeal metastases from breast cancer and NSCLC.",[26,27,28,29,30],"2026-06-15",{"date":87,"type":35},{"date":330,"type":35},"2025-03-03",{"date":332,"type":20},"2028-07-01",{"name":334,"class":42},"University of Washington",2,{"id":337,"slug":4,"hasResults":11,"nctId":338,"briefTitle":339,"officialTitle":340,"acronym":4,"eligibilityCriteria":341,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":342,"targetDuration":4,"studyType":21,"phases":344,"briefSummary":345,"conditions":346,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":327,"lastUpdatePostDateStruct":347,"startDateStruct":348,"completionDateStruct":350,"leadSponsor":351,"locationsCount":114},"100483114","NCT05570825","SX-682 With Pembrolizumab for the Treatment of Metastatic or Recurrent Stage IIIC or IV Non-Small Cell Lung Cancer","A Phase 2 Trial of SX-682 and Pembrolizumab in Patients With Treatment Naive Stage IV or Recurrent Non-Small Cell Lung Cancer","Inclusion Criteria:\n\n* Subjects aged 18 years and older\n* Pathologically or cytologically confirmed non-small cell lung cancer with no known oncogenic EGFR mutation, ALK rearrangement, ROS1 rearrangement or RET rearrangement\n* Tumoral PD-L1 expression \\>=1% by any Clinical Laboratory Improvement Act (CLIA)-certified assay\n* Metastatic or recurrent non-small cell lung cancer (NSCLC). Stage IIIC per 8th edition TNM stage classification is allowed if not amenable to curative surgery or radiation per investigator judgment\n* At least one site of measurable disease as determined by the Investigator, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. Subjects must have ECOG PS 0 or 1 at the time of informed consent and at the time of treatment initiation\n* Must be willing to provide pre-treatment archived specimen or undergo a biopsy procedure if archived specimen is not available\n* Must be willing to provide an on-treatment biopsy, if deemed safe by the treating physician\n* Platelet count \\>= 100,000\u002FuL\n* Absolute neutrophil count \\>= 1,500\u002FuL\n* Hemoglobin \\>= 8g\u002FdL\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\\\u003C 2.5 times upper limit of normal\n* Creatinine =\\\u003C 2.0 mg\u002FdL\n* Women of child-bearing potential and sexually active men must agree to use adequate contraception (hormonal or barrier method) prior to treatment initiation, during treatment and for three months after completing treatment\n* Negative beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of childbearing potential. Pregnant or breast feeding women are not eligible\n* Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment\n\nExclusion Criteria:\n\n* Participants must not have received prior chemotherapy or immune checkpoint inhibitor or immune-modulatory therapy (e.g. anti-PD\\[L\\]1, anti-CTLA4, anti-TIM3, anti-GITR, anti-TIGIT, anti-LAG3), for metastatic or recurrent NSCLC, with the following exceptions:\n\n  * Participants may have received prior chemotherapy, immune checkpoint inhibitor, and\u002For immune modulatory therapy in the curative setting if the last dose of treatment was more than (\\>) 24 weeks prior to consenting\n  * For patients with NSCLC harboring an oncogenic alteration other than listed may have received prior small molecule inhibitor therapy (e.g. MET inhibitor for MET exon 14 mutated NSCLC). A wash-out period of at least 5 half-lives is required prior to start of study treatment\n* Presence of other active cancers within the last 2 years. Patients with any prior early stage cancer who have received definitive local treatment at least 2 years previously and no evidence of recurrence are eligible. All patients with previously treated in situ carcinoma are eligible, as patients with history of non-melanoma skin cancer\n* Symptomatic central nervous system (CNS) metastases; participants with known brain metastasis must be asymptomatic with no steroids or escalating doses of antiepileptics within 7 days prior to start of study treatment\n\n  * Patients with untreated CNS metastases may be enrolled as long as they meet the above criteria. Patients with bulky CNS metastases should consider receiving radiation prior to study entry per investigator judgment\n* Participants with spinal cord compression must have received local treatment and must have been symptomatically stable with no use of steroids for at least 7 days prior to start of study treatment\n* Participants must not have an active autoimmune disease that has required immune modulating treatment within (\\\u003C) 365 days prior to consenting (i.e., disease modifying agents, corticosteroids). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed\n* Inability to discontinue systemic corticosteroid therapy; systemic steroids must be tapered off 7 days prior to first dose of SX-682\n* Known history of primary immunodeficiency\n* History of organ transplant that requires use of immunosuppressives\n* Current symptomatic pneumonitis and any past history of immune checkpoint inhibitor related pneumonitis regardless of steroid treatment history\n* History of non-infectious pneumonitis (e.g. radiation pneumonitis) that required steroids within 3 months of start of study treatment\n* Radiotherapy within 7 days of start of study treatment\n* Major surgery within 21 days of start of study treatment. Minor surgery within 2 weeks of start of study treatment. Placement of vascular access device and biopsies are not considered major or minor surgery and are allowed\n* Electrocardiogram (EKG) demonstrating a corrected QT (QTc) interval \\> 480 msec on three consecutive EKGs or patients with congenital long QT syndrome\n* Severe lung disease (e.g. chronic obstructive pulmonary disease \\[COPD\\]) who cannot stop steroids 7 days prior to start of study treatment\n* Serious cerebrovascular and cardiac disease defined as:\n\n  * Active unstable angina pectoris\n  * Congestive heart failure NYHA (New York Heart Association) \\> grade 3\n  * Acute myocardial infarction within 3 months of consenting\n  * Stroke or transient ischemic attack within 3 months of consenting\n* Known active chronic infections: Active hepatitis B, hepatitis C and tuberculosis. Testing is not required for assessment of eligibility. Active infection requiring IV antibiotics within 7 days of study treatment initiation\n\n  * Hepatitis C virus (HCV) infection: Patients with known history of HCV infection are eligible if HCV viral load is below the limit of quantification per local assay\n  * Hepatitis B virus (HBV) infection: Patients with known history of HBV infection are eligible if HBV viral load is below the limit of quantification and negative hepatitis B virus surface antigen (HBsAg) per local assay\n* Known uncontrolled HIV (human immunodeficiency virus) infection\n\n  * Participants with known HIV infection are allowed if they are receiving anti-retroviral therapy, have CD4+ T-cell count \\>= 350 cells\u002FuL within 6 months prior to study treatment initiation and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection\n* Any serious or uncontrolled concomitant disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study\n* Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent",{"count":343,"type":20},30,[78],"This phase II trial tests whether CXCR1\u002F2 inhibitor SX-682 (SX-682) with pembrolizumab works to treat patients with stage IIIC or IV non-small cell lung cancer that has spread to other parts of the body (metastatic) or that has come back (recurrent). SX-682 is a drug that binds to receptors on some types of immune and cancer cells, inhibiting signaling pathways, reducing inflammation, and allowing other types of immune cells to kill and eliminate cancer cells. Pembrolizumab is a monoclonal antibody that binds to a receptor called PD-1 that is found on the surface of T-cells (a type of immune cell), activating an immune response against tumor cells. Giving SX-682 in combination with pembrolizumab may be more effective at treating patients with metastatic or recurrent non-small cell lung cancer than giving these treatments alone.",[28,267,129,30],{"date":87,"type":35},{"date":349,"type":35},"2023-04-06",{"date":332,"type":20},{"name":334,"class":42},{"id":353,"slug":4,"hasResults":11,"nctId":354,"briefTitle":355,"officialTitle":356,"acronym":4,"eligibilityCriteria":357,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":358,"targetDuration":4,"studyType":21,"phases":360,"briefSummary":362,"conditions":363,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":372,"lastUpdatePostDateStruct":373,"startDateStruct":375,"completionDateStruct":377,"leadSponsor":379,"locationsCount":114},"100624088","NCT07405086","Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study","Knight Cancer Institute Study of Histology-Agnostic Immunotherapy With Focus on Timing: - Knight SHIFT - A Prospective, Multi-Histology Pragmatic Study","Inclusion Criteria:\n\n* Must provide written informed consent before any study-specific procedures or interventions are performed\n* Aged ≥ 18 years\n* Histologically confirmed advanced\u002Fmetastatic solid tumor as follows:\n\n  * Non small cell lung cancer (NSCLC) (driver-negative, immune checkpoint inhibitor \\[ICI\\]-eligible)\n  * Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) (platinum-eligible),\n  * Renal cell carcinoma (RCC)\n  * Biliary-tract cancer (BTC)\n  * Hepatocellular carcinoma (HCC)\n  * Melanoma\n* Planned to receive a Food and Drug Administration (FDA)-approved immune check point inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4) regimen for the treatment of their malignancy\n* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n\nExclusion Criteria:\n\n* Prior ICI-based regimen for treatment of cancer\n* Current or prior use of immunosuppressive medication within 28 days before planned standard-of-care immunotherapy infusion, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses not exceeding 10 mg\u002Fday of prednisone (or equivalent corticosteroid)\n* Uncontrolled autoimmune disease requiring immunosuppression\n* Active, uncontrolled central nervous system (CNS) metastases",{"count":359,"type":20},160,[361],"PHASE4","This phase IV trial is evaluating whether morning versus afternoon administration of standard of care immunotherapy impacts its effectiveness in treating patients with solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Circadian rhythm refers to the internal biological clock in which various processes in the body, including immune cell activity, are controlled by the time of day. Exactly how this works is not fully understood, and the researchers want to see if circadian rhythm control of the immune system can influence response to immunotherapy based on whether it is given in the morning (before 11:00 am) or afternoon (12:00pm). The time of day that immunotherapy is given (morning versus afternoon) may impact the effectiveness in treating patients with advanced or metastatic solid tumors.",[364,365,366,105,367,368,369,370,188,189,28,57,58,59,371,196,82,197,210,30,60],"Advanced Biliary Tract Carcinoma","Advanced Head and Neck Squamous Cell Carcinoma","Advanced Hepatocellular Carcinoma","Advanced Malignant Solid Neoplasm","Advanced Melanoma","Advanced Renal Cell Carcinoma","Metastatic Biliary Tract Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","2026-06-10",{"date":374,"type":35},"2026-06-12",{"date":376,"type":35},"2026-06-08",{"date":378,"type":20},"2028-12-31",{"name":380,"class":42},"OHSU Knight Cancer Institute",{"id":382,"slug":4,"hasResults":11,"nctId":383,"briefTitle":384,"officialTitle":385,"acronym":4,"eligibilityCriteria":386,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":387,"targetDuration":4,"studyType":21,"phases":389,"briefSummary":390,"conditions":391,"keywords":4,"overallStatus":130,"whyStopped":4,"lastUpdateSubmitDate":392,"lastUpdatePostDateStruct":393,"startDateStruct":394,"completionDateStruct":396,"leadSponsor":398,"locationsCount":114},"100617724","NCT07322341","SX-682 and Atezolizumab for the Treatment of Advanced or Metastatic, Recurrent Non-small Cell Lung Cancer","A Phase 2 Trial of SX-682 and Atezolizumab in Patients With Advanced NSCLC Who Progressed on Prior Chemotherapy and Immune Checkpoint Inhibitor (ICI) Therapy","Inclusion Criteria:\n\n* Age 18 years and older\n* Ability to understand and willingness to sign a written informed consent document\n* Pathologically or cytologically confirmed non-small cell lung cancer with no known oncogenic EGFR mutation, ALK fusion, ROS1 fusion or RET fusions.\n\n  * For participants with NSCLC harboring an oncogenic alteration other than the above must have received prior targeted therapy (e.g. small molecule inhibitor therapy or antibody drug conjugates). A wash-out of at least 5 half-lives is required prior to start of study treatment\n* Metastatic or recurrent NSCLC. Stage 3C per 8th edition TNM stage classification is allowed if not amenable to curative surgery or radiation per investigator judgment\n* Participants must have received and progressed on at least 6 weeks of treatment with prior anti-PD-1 or anti-PD-L1 therapy for advanced disease. Also, participants must have received prior platinum doublet chemotherapy. Anti-PD1\u002FPD-L1 therapy may have been received concurrently with chemotherapy or as sequential therapy (e.g. anti-PD1 followed by chemotherapy).\n\n  * For participants who received neoadjuvant, adjuvant and\u002For consolidation anti-PD-1 or anti-PD-L1 therapy for stage 1 - 3 NSCLC: If they experienced disease progression ≤ 365 days from initiation of anti-PD-1 or anti-PD-L1 therapy, this counts as the allowed anti-PD-1 or anti-PD-L1 therapy for advanced disease.\n  * For participants who experienced disease progression more than 365 days from initiation of anti-PD-1 or anti-PD-L1 therapy for advanced disease, this is not considered anti-PD-1 or anti-PD-L1 therapy for advanced disease. These patients must have received anti-PD-1 or anti-PD-L1 therapy for stage 4 or recurrent disease\n* Participants must have a minimum of 28 days after the last dose, or 5 half-lives of washout period (whichever is shorter) from last dose of most recent systemic therapy prior to initiation of study treatment, including investigational agents\n* Participants must have at least one site of measurable disease as determined by the investigator, using RECIST v 1.1 criteria documented within 28 days prior to study treatment initiation\n* Participants must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 at the time of informed consent and at the time of treatment initiation\n* Participants must be willing to provide pre-treatment archived specimen (taken within a year of trial entry) or undergo a biopsy procedure if archived specimen is not available.\n\n  * If biopsy is not deemed safe, it may be waived after discussion with principal investigator (PI)\n* Participants must be willing to provide an on-treatment biopsy, to be obtained at 6 - 9 weeks, if deemed safe by the treating physician\n* Platelet count \\> 100,000\u002FμL\n* Absolute neutrophil count \\> 1,500\u002FμL\n* Hemoglobin \\> 9.0 g\u002FdL. Participants may be transfused to meet this criterion\n* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) \\\u003C 2.5 times upper limit of normal\n* Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) with the following exception: Patients with known Gilbert disease: serum bilirubin ≥ 3 x ULN\n* Creatinine clearance ≥ 30 mL\u002Fmin\n* For patients not receiving therapeutic anticoagulation: International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN\n* For patients receiving therapeutic anticoagulation: stable anticoagulant regimen\n* Participants of child-bearing potential and sexually active men must agree to use adequate contraception (hormonal methods must be supplemented by barrier method) prior to treatment initiation, during treatment, and for 5 months after the last dose of atezolizumab\n* Negative beta human chorionic gonadotropin (β-hCG) pregnancy test result within 14 days prior to initiation of study treatment for participants of childbearing potential. Pregnant or breast-feeding women or intention of becoming pregnant during study treatment or within 5 months of last dose of atezolizumab are not eligible\n\nExclusion Criteria:\n\n* Presence of other active cancers within the last 2 years. Participants with another cancer who have received definitive therapy at least 2 years previously and no evidence of recurrence are eligible. All participants with previously treated in situ carcinoma are eligible, as are participants with history of non-melanoma skin cancer\n* Symptomatic central nervous system (CNS) metastases; participants with known brain metastasis must be asymptomatic with no ongoing requirement for steroids within 7 days prior to start of study treatment, no history of intracranial hemorrhage or spinal cord hemorrhage. If the patient is receiving anti-convulsant therapy, the dose is considered stable\n\n  * Participants with untreated CNS metastases may be enrolled as long as they meet the above criteria. Participants with bulky CNS metastases should consider receiving radiation prior to study entry per investigator judgment\n* Participants with spinal cord compression must have received local treatment and must have been symptomatically stable with no use of steroids for at least 7 days prior to start of study treatment\n* Participants must not have an active autoimmune disease that has required immune modulating treatment within 1 year prior to consenting (i.e., disease modifying agents, long term corticosteroids). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed. Short-term steroid therapy (≤ 2 weeks) is allowed\n* Inability to discontinue corticosteroid therapy; steroids must be tapered off 7 days prior to first dose of SX-682. Limited steroid use for allergic reactions is acceptable\n* Known history of primary immunodeficiency\n* History of organ transplant or prior allogenic stem cell transplantation that requires use of immunosuppressives\n* Current symptomatic pneumonitis and any past history of immune checkpoint inhibitor related pneumonitis regardless of steroid treatment history\n* Prior history of grade 3 or higher immune checkpoint inhibitor (ICI)-induced immune-related adverse event (AE) (immune related adverse event \\[irAE\\]) except endocrine irAEs that are resolved or managed with replacement therapy\n* Radiotherapy within 7 days of start of study treatment\n* Major surgery within 21 days of start of study treatment. Minor surgery within 2 weeks of start of study treatment.\n\n  * Placement of vascular access device and biopsies are not considered major or minor surgery and are allowed\n* Electrocardiogram (ECG) demonstrating a Fridericia's corrected QT interval (QTcF) interval \\> 480 msec or patients with congenital long QT syndrome\n* Severe lung disease (e.g. chronic obstructive pulmonary disease \\[COPD\\]) who cannot stop steroids 7 days prior to start of study treatment\n* Serious cerebrovascular and cardiac disease defined as:\n\n  * Active unstable angina pectoris\n  * Congestive heart failure New York Heart Association (NYHA) \\> grade 3\n  * Acute myocardial infarction within 3 months of consenting\n  * Stroke or transient ischemic attack within 3 months of consenting\n* Known active chronic infections: Active hepatitis B, hepatitis C and tuberculosis. Testing is not required for assessment of eligibility per investigator judgment. Active infection requiring IV antibiotics within 7 days of study treatment initiation.\n\n  * Hepatitis C virus (HCV) infection: Patients with known history of HCV infection are eligible if HCV viral load is below the limit of quantification per local assay per investigator judgment.\n  * Hepatitis B virus (HBV) infection: Patients with known history of HBV infection are eligible if HBV viral load is below the limit of quantification and negative hepatitis B surface antigen (HBsAg) per local assay per investigator judgment\n* Known uncontrolled HIV (human immunodeficiency virus) infection\n\n  * Participants with known HIV infection are allowed if they are receiving anti-retroviral therapy, have CD4+ T-cell count \\> 350 cells\u002FµL within 6 months prior to study treatment initiation and no history of AIDS- defining opportunistic infection\n* Any serious or uncontrolled concomitant disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study\n* Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent\n* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab\n* History of leptomeningeal disease\n* Treatment with investigational therapy within 28 days prior to initiation of study treatment, or 5 half-lives of washout period (whichever is shorter) from last dose of most recent systemic therapy\n* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins\n* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation\n* Known allergy or hypersensitivity to any component of the atezolizumab formulation",{"count":388,"type":20},32,[78],"This phase II trial tests how well SX-682 and atezolizumab works for the treatment of non-small cell lung cancer (NSCLC) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic), and has come back after a period of improvement (recurrent). SX-682 blocks proteins that may be able to stimulate the immune system to kill and eliminate tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving SX-682 and atezolizumab may be effective for the treatment of advanced or metastatic, recurrent NSCLC.",[105,28,267,82,30],"2026-06-04",{"date":376,"type":35},{"date":395,"type":20},"2026-09-01",{"date":397,"type":20},"2031-11-01",{"name":334,"class":42},{"id":400,"slug":4,"hasResults":11,"nctId":401,"briefTitle":402,"officialTitle":403,"acronym":4,"eligibilityCriteria":404,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":405,"targetDuration":4,"studyType":21,"phases":407,"briefSummary":408,"conditions":409,"keywords":4,"overallStatus":130,"whyStopped":4,"lastUpdateSubmitDate":411,"lastUpdatePostDateStruct":412,"startDateStruct":414,"completionDateStruct":416,"leadSponsor":418,"locationsCount":114},"100641026","NCT07619599","A PET Imaging Agent (64Cu-DOTA-Pembrolizumab) for Determining Treatment Response Among Patients With Stage IV Non-small Cell Lung Cancer Receiving Pembrolizumab","Pilot Study of 64Cu-DOTA Pembrolizumab (64CDP) in Patients Receiving Stereotactic Body Radiation Therapy (SBRT) for Oligo-Progressive Non-Small Cell Lung Cancer (NSCLC)","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative\n\n  * Assent, when appropriate, will be obtained per institutional guidelines\n* Age: ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) ≤ 2\n* Histologically confirmed stage IV non-small cell lung cancer\n* Patients on single-agent pembrolizumab, who have been referred for SBRT for or oligo-progressive disease. A maximum of 6 sites will be allowed to receive SBRT on protocol\n* Patients must have sites that are amenable to SBRT that are located in lymph nodes, bone\u002Fspine, or lung\n* Brain metastases or cases with intra-cranial progression are allowed, but an additional extra-cranial site planned for SBRT is required\n* Absolute neutrophil count (ANC) ≥ 1,000\u002Fmm\\^3\n* Platelets ≥ 50,000\u002Fmm\\^3\n\n  * NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment\n* Total bilirubin ≤ 1.5 X upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) ≤ 3.0 x ULN\n* Alanine aminotransferase (ALT) ≤ 3.0 x ULN\n* Creatinine clearance of ≥ 30 mL\u002Fmin per 24 hour urine test or the Cockcroft-Gault formula\n* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test\n\n  * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* Agreement by females and males of childbearing potential\\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy\n\n  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \\> 1 year (women only)\n\nExclusion Criteria:\n\n* Patient planned to stop pembrolizumab at time of referral for SBRT\n* Vaccination with live attenuated vaccines within 4 weeks of study agent administration except forthcoming coronavirus disease 2019 (COVID-19) and flu vaccines\n* Subject is currently using or has used immunosuppressive medication within 14 days prior to the study agent administration with the exception of:\n\n  * Intranasal, topical, inhaled, or local steroid injections (e.g., intra-articular injection)\n  * Chronic systemic corticosteroids at physiologic doses not to exceed 5 mg\u002Fday of prednisone or equivalent\n  * Steroids as premedication for hypersensitivity reactions (e.g., infusion-related reactions, CT scan premedication)\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent\n* Clinically significant uncontrolled illness\n* Infection requiring systemic antibiotic therapy within 14 days prior to start of study treatment\n* Patient unable to tolerate PET scan even with anxiolytic medications\n* Other active metastatic malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Females only: Pregnant or breastfeeding\n* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures\n* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility\u002Flogistics)",{"count":406,"type":20},6,[77],"This phase I trial studies the safety and side effects of a new positron emission tomography (PET) imaging agent called 64Cu-DOTA-pembrolizumab to see how well it works in determining treatment response for patients with stage IV non-small cell lung cancer (NSCLC) already receiving pembrolizumab. 64Cu-DOTA-pembrolizumab consists of a monoclonal antibody, pembrolizumab, that binds to a protein called PD-1 that is expressed on tumor cells. PET scans can then visualize the tumor cells using 64Cu, a radioactive substance. 64Cu-DOTA-pembrolizumab PET scans may be safe and useful to doctors in telling the difference between tumors that are still growing and areas that are not growing in patients with stage IV NSCLC receiving pembrolizumab treatment.",[28,56,410,30],"Oligoprogressive Lung Non-Small Cell Carcinoma","2026-05-26",{"date":413,"type":35},"2026-06-02",{"date":415,"type":20},"2026-09-14",{"date":417,"type":20},"2028-12-22",{"name":419,"class":42},"City of Hope Medical Center",{"id":421,"slug":4,"hasResults":11,"nctId":422,"briefTitle":423,"officialTitle":424,"acronym":4,"eligibilityCriteria":425,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":426,"targetDuration":4,"studyType":21,"phases":428,"briefSummary":429,"conditions":430,"keywords":4,"overallStatus":130,"whyStopped":4,"lastUpdateSubmitDate":434,"lastUpdatePostDateStruct":435,"startDateStruct":437,"completionDateStruct":439,"leadSponsor":441,"locationsCount":4},"100591576","NCT06982222","Testing the Safety of the Anti-cancer Drug, Sn-117m-DTPA, for Advanced Cancers That Have Spread to Bones","A First-in-Human Dose-Finding Phase I Study of Bone-targeted High Specific Activity Stannic-117m Pentatate (Sn-117m-DTPA) in Solid Tumors With Skeletal Metastases","Inclusion Criteria:\n\n* Histologically documented prostate, breast, or non-small cell lung cancer (NSCLC)\n* Metastatic disease in bone only (patients with visceral disease, cutaneous disease or malignant lymph nodes \\> 3 cm in largest diameter are not eligible)\n* Documented disease progression (1 or more new bone lesion or enlargement of existing bone lesion, identified by Tc-99m bone scintigraphy or CT scan, magnetic resonance imaging \\[MRI\\], fludeoxyglucose F-18 \\[FDG\\] PET CT scan or PSMA PET CT scan)\n* Must have progression on at least one line of standard of care systemic therapy. There are no maximum number of prior therapies\n* Patients with prostate cancer\n\n  * Patients with prostate adenocarcinoma, their disease must be characterized as: must have prior bilateral orchiectomy or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (\\\u003C 50 ng\u002FdL or \\\u003C 1.7 nmol\u002FL)\n  * Serum PSA progression, defined as two consecutive increases in PSA over a previous reference value, each measurement at least one week apart or, PSA progression ≥ 25% after 12 weeks of current standard of care (SOC) therapy (Scher et al., 2016)\n  * Patients must have a baseline positive PSMA-PET scan. Patients must have progressed on at least one line of hormone therapy: Androgen receptor signaling inhibitors (ARSIs) therapy such as enzalutamide, apalutamide, darolutamide, or androgen synthesis blockers (abiraterone acetate). There are no minimum number of prior hormone therapies\n  * Progression after chemotherapy (docetaxel or cabazitaxel) in patients who were chemotherapy candidates is allowed. However, prior chemotherapy is not required\n  * Progression after a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy (for example: lutetium-177 vipivotide tetraxetan \\[Pluvicto\\]) is allowed but not required\n  * Allowed to have received one prior cytotoxic chemotherapy treatment and one radiopharmaceutical therapy treatment OR no more than two cytotoxic chemotherapy treatments (for patients who have not received a prior radiopharmaceutical therapy treatment)\n* Patients with breast cancer\n\n  * Patients with any estrogen receptor (ER)\u002Fprogesterone receptor (PR)\u002Fhuman epidermal growth factor receptor 2 (HER2) receptor status are eligible\n  * Patients with hormone-receptor positive disease should have progressed on at least one or more prior line(s) of SOC anti-estrogen therapy and a cyclin-dependent kinase (CDK)4\u002F6 inhibitor (except if patient had a contraindication or intolerable toxicity with the use of these agents)\n  * Patients with HER2 positive disease should have progressed on at least one or more line(s) of SOC anti-HER2 therapy.\n  * Patients with triple negative disease should have progressed on at least one more line(s) of SOC chemotherapy\n  * Previous radiation and chemotherapy are allowed\n* Patients with non-small cell lung cancer (NSCLC)\n\n  * Patients with NSCLC should have progressed on at least one or more prior line(s) of SOC therapy, including chemotherapy and\u002For immunotherapy or targeted therapy if they qualify\n* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of Sn-117m-DTPA in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)\n* Absolute neutrophil count ≥ 1,000\u002FmcL\n* Platelets ≥ 75,000\u002FmcL\n* Hemoglobin \\> 9 g\u002FdL\n* Total bilirubin ≤ 2.5 x institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 5 x institutional ULN\n* Creatinine ≤ 1.7 mg\u002FdL OR glomerular filtration rate (GFR) ≥ 50 mL\u002Fmin\u002F1.73 m\\^2\n* Patients must be taking a bone health agent (bisphosphonates or denosumab) for at least one (1) month prior to enrollment\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better\n* The effects of Sn-117m-DTPA on the developing human fetus are unknown. For this reason and because radionucleotides are known to be teratogenic, male participants and their female partners of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. A woman of childbearing potential is a premenopausal female capable of becoming pregnant. Should a woman of childbearing potential become pregnant or suspect she is pregnant while her male partner is participating in this study, she should inform her treating physician immediately. Both men and women of childbearing potential treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after completion of Sn-117m-DTPA administration. For prostate cancer patients, androgen deprivation therapy is considered adequate contraception\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign if the patient is physically (not mentally) not capable of signing\n\nExclusion Criteria:\n\n* Patients who have not recovered from reversible adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia\n* Patients must not have received any investigational agents within 4 weeks or 5 half-lives, whichever is shorter, before starting study treatment, nor be scheduled to receive one during the planned treatment period\n* Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Sn-117m-DTPA\n* Patients must not have imminent or established spinal cord compression, pathological fracture in weight bearing bones, or bone lesion with soft tissue component unless treated as appropriate with radiation and\u002For surgery before starting on this study\n* Patients must not have received prior systemic radiotherapy with strontium-89, samarium-153, rhenium-186, rhenium-188, or radium-223 dichloride (Xofigo) for the treatment of bony metastases. Prior systemic radiopharmaceutical therapy with lutetium Lu 177 vipivotide tetraxetan (Pluvicto) is permitted, but last treatment must be at least six weeks prior to starting study treatment due to the concern of bone marrow suppression\n* Patients must not have unmanageable urinary incontinence\n* Pregnant women are excluded from this study because Sn-117m-DTPA is a radionucleotide with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Sn-117m-DTPA, breastfeeding should be discontinued if the mother is treated with Sn-117m-DTPA",{"count":427,"type":20},24,[77],"This phase I trial tests the safety, side effects and best dose of tin (Sn)-177m-diethylenetriaminepentaacetic acid (DTPA) and how well it works in treating prostate, breast or non-small cell lung cancer that has spread from where it first started (primary site) to the bones (bone metastases). Sn-117m-DTPA was originally tested in tumors that had spread to the bones to help reduce bone pain. The drug has been improved and is designed to send low-level radiation to tumors in the bone while being gentler on the bone marrow, where blood cells are made. Sn-117m-DTPA may be safe and tolerable, and may slow down or shrink tumors in patients with metastatic prostate, breast, or non-small cell lung cancer that has spread to the bones.",[26,27,28,431,432,30,433],"Metastatic Malignant Neoplasm in the Bone","Metastatic Prostate Adenocarcinoma","Stage IVB Prostate Cancer AJCC v8","2026-05-12",{"date":436,"type":35},"2026-05-13",{"date":438,"type":20},"2026-10-01",{"date":440,"type":20},"2027-02-12",{"name":91,"class":92},{"id":443,"slug":4,"hasResults":11,"nctId":444,"briefTitle":445,"officialTitle":446,"acronym":4,"eligibilityCriteria":447,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":448,"targetDuration":4,"studyType":21,"phases":450,"briefSummary":451,"conditions":452,"keywords":4,"overallStatus":130,"whyStopped":4,"lastUpdateSubmitDate":472,"lastUpdatePostDateStruct":473,"startDateStruct":475,"completionDateStruct":476,"leadSponsor":478,"locationsCount":114},"100638080","NCT07576725","Low Dose, Reduced Frequency Nivolumab for the Treatment of Unresectable or Metastatic Cancer, AFFORD IO Trial","AFFORD IO: A Phase 2 Trial of Low Dose, Reduced Frequency Nivolumab (Anti-PD-1 Antibody) in Patients With Unresectable or Metastatic Cancer","Inclusion Criteria:\n\n* Participants are eligible if they have one of these histologically confirmed, unresectable or metastatic cancer types listed below, based upon historical responsiveness to anti-PD-(L)1 agents\n\n  * Non-small cell lung cancer (NSCLC) with documented PD-L1 expression (combined positive score \\[CPS\\] ≥ 1) (NOTE: Participants with known driver oncogenic mutations\u002Frearrangements, including EGFR, ALK and ROS-1, will be excluded.)\n  * Head and neck squamous cell carcinoma (HNSCC) with documented PD-L1 expression (CPS ≥ 1)\n  * Clear cell renal cell carcinoma (ccRCC) (NOTE: Other subtypes may be permitted after approval by the Medical Monitor)\n  * Melanoma (cutaneous, acral-lentiginous and mucosal subtypes), and non-melanoma skin cancers, (cutaneous squamous cell carcinoma \\[CSCC\\], basal cell carcinoma \\[BCC\\] and Merkel cell carcinoma \\[MCC\\])\n  * Hodgkin's lymphoma\n  * Urothelial carcinoma\n  * Cervical cancer with documented PD-L1 expression (CPS ≥ 1)\n  * Colorectal cancer with high microsatellite instability (MSI) or mismatch repair deficiency\n  * Kaposi sarcoma (KS) without clinical concern for multicentric Castleman's disease (MCD)\n  * Any cancer type with historical data suggesting an ORR \\> 20% with anti-PD(L)-1 agents (NOTE: All participants in this category must be approved by the Medical Monitor prior to enrollment.)\n* Must have experienced disease progression after or deemed not to be a good candidate for available curative systemic therapy options\n* Presence of at least one measurable tumor, per RECIST v1.1\n* Age 18 or older. (NOTE: Both men and women, and members of all races and ethnic groups are eligible for this trial.)\n* Eastern Cooperative Oncology Group (ECOG) performance score of 0-2\n* Absolute neutrophil count (ANC) ≥ 1.0 × 10\\^9\u002FL\n* Platelet count ≥ 75 × 10\\^9\u002FL\n* Hemoglobin ≥ 9 g\u002FdL (NOTE: Participants may have been transfused)\n* Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) (or total bilirubin ≤ 2.5 × upper limit of normal \\[ULN\\] in participants with Gilbert's syndrome)\n* Estimated creatinine clearance ≥ 30mL\u002Fmin according to the Cockcroft-Gault formula or according to local institutional standard\n* Must consent to undergo serial research blood draws at study defined timepoints, unless deemed unsafe or not feasible by the treating investigator\n* Must have an ability to understand and provide consent to the institutional review board (IRB)-approved informed consent form (ICF) document(s)\n* Women of childbearing potential must have a negative serum or urine pregnancy test at screening\n* Both male and female participants must be willing to use highly effective contraception, as stipulated in national or local guidelines, throughout the study and for at least 180 days after the last treatment administration, if the risk of conception exists\n\nExclusion Criteria:\n\n* Prior exposure to any immune-checkpoint inhibitor for any reason\n* Residual adverse event(s) from prior therapy grade \\> 1 (National Cancer Institute \\[NCI\\]-Common Terminology Criteria for Adverse Events \\[CTCAE\\] v6.0) that could interfere with study endpoints or put participant safety at risk, as determined by the treating investigator\n* Known active central nervous system (CNS) metastases and\u002For prior history of leptomeningeal cancer involvement\n* Known history of another active malignancy (besides the eligible cancer diagnosis) within the last 3 years from day 1 of nivolumab that could interfere with study endpoints or put participant safety at risk. (NOTE: Exception will be made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ \\[skin, bladder, cervical, colorectal, breast\\] or low grade prostatic intraepithelial neoplasia or grade 1 prostate cancer. Any other neoplasm, which has been treated adequately and is adjudged by the treating investigator to have a low risk of progression during the study, could be enrolled only after approval from the medical monitor.)\n* Known active hepatitis B virus (HBV) or hepatitis C virus (HCV), defined as follows:\n\n  * Active HBV is defined as a known positive hepatitis B virus surface antigen (HBsAg) result or positive total hepatitis B virus core antibody (anti-HBc) results in the absence of hepatitis B virus surface antibody (anti-HBsAb). (NOTE: When HBsAg is negative and HBcAb is positive, HBV-DNA should be measured. When HBV-deoxyribonucleic acid \\[DNA\\] is negative, this participant could be enrolled with close monitoring of HBV activities.)\n  * Active hepatitis C virus (HCV) is defined as a known positive HCV antibody result and quantitative HCV-ribonucleic acid (RNA) results greater than the lower limits of detection of the assay. (NOTE: Participants who have had definitive treatment for HCV are permitted if HCV-RNA is undetectable.)\n* Known uncontrolled HIV infection. (NOTE: HIV-infected participants may be allowed if all the following criteria are met: CD4 count ≥ 100\u002FμL, viral load less than 200 copies\u002FmL, and clinically stable on antiretroviral therapy \\[ART\\] for at least 3 months.)\n\n  * These participants will be enrolled only after approval from the medical monitor\n* Known active autoimmune disease or an allograft requiring systemic immunosuppression with corticosteroids (\\> 10 mg\u002Fday of prednisone or equivalent) or immunosuppressive drugs within the past 2 years before the first dose of nivolumab. (NOTE: Exceptions will be made for participants with autoimmune conditions such as diabetes type I, vitiligo, psoriasis, hypothyroid or hyperthyroid diseases not requiring immunosuppressive treatment; participants receiving physiologic corticosteroid replacement therapy at doses \\\u003C 10 mg\u002Fday of prednisone or equivalent for adrenal or pituitary insufficiency; participants with a condition such as asthma or chronic obstructive pulmonary disease that requires intermittent use of steroids or those who require brief courses of corticosteroids for prophylaxis \\[e.g., contrast dye allergy\\], nivolumab-related standard premedication, and\u002For treatment of non-serious immune related adverse events. Any other situation must be discussed with the medical monitor for risk\u002Fbenefit assessment.)\n* Immunosuppressed status due to severe uncontrolled diabetes, concurrent uncontrolled hematological malignancy, or other comorbidities\n* Known history of serious, active infections (aside from well-controlled HIV, as per exclusion criterion #6) requiring systemic antimicrobial agents within 14 days before the first dose of nivolumab. (NOTE: Chronic infections such as herpes simplex virus requiring suppressive therapy may be allowed after discussion with the medical monitor for risk\u002Fbenefit assessment.)\n* Known history of clinically significant interstitial lung disease, or active noninfectious pneumonitis\n* Clinically significant (i.e., active) cardiovascular disease such as cerebral vascular accident or myocardial infarction within 6 months prior to first dose of nivolumab, ongoing unstable angina or congestive heart failure (New York Heart Association Classification class II-IV), or serious cardiac arrhythmia that could jeopardize participant safety on the study\n* Receipt of live vaccine(s) within 30 days of planned start of nivolumab. (NOTE: Examples of live vaccines include but are not limited to measles, mumps, rubella, varicella-zoster \\[chickenpox\\], yellow fever, rabies, bacillus Calmette Guerin \\[BCG\\], and typhoid vaccines. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines are live, attenuated vaccines and are not allowed.)\n* Known severe acute or chronic medical conditions such as uncontrolled seizure disorder, serious psychiatric illness, or laboratory abnormalities, that may increase the risk associated with study participation or may interfere with the interpretation of study endpoints and, in the judgment of the treating investigator, would make the participant inappropriate for entry into this study\n* Known active tuberculosis (TB). (NOTE: Participants with latent TB will be allowed, provided they are receiving tuberculosis preventive therapy, after approval of the medical monitor.)\n* Known allergy or hypersensitivity to any component of the study drug formulation (including excipients and additives) that could interfere with study endpoints or put participant safety at risk\n* Pregnant or breast-feeding woman",{"count":449,"type":20},50,[78],"This phase II trial studies how well low dose, reduced frequency nivolumab works in treating patients with cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Nivolumab is a type of immune checkpoint inhibitor (ICI). ICIs have revolutionized the treatment of numerous cancers with remarkable improvement in participant outcomes. However, accessibility of ICIs is extremely poor on a global scale, mainly due to high costs. Previous research has suggested that these drugs can be given at lower doses and reduced frequency than their approved dosing regimens, with similar results. Giving nivolumab at a lower dose and less often may help reduce the cost of therapy, improve immunotherapy accessibility, and therefore improve survival outcomes globally.",[154,453,158,454,455,456,457,458,184,459,460,461,188,462,28,57,190,463,191,193,195,464,237,82,197,208,465,238,30,60,466,467,220,468,469,470,224,226,227,229,471,231,233],"Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8","Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8","Hodgkin Lymphoma","Kaposi Sarcoma","Metastatic Acral Lentiginous Melanoma","Metastatic Basal Cell Carcinoma","Metastatic Clear Cell Renal Cell Carcinoma","Metastatic Colorectal Carcinoma","Metastatic Cutaneous Melanoma","Metastatic Kaposi Sarcoma","Metastatic Mucosal Melanoma","Stage III Colorectal Cancer AJCC v8","Stage IV Colorectal Cancer AJCC v8","Unresectable Acral Lentiginous Melanoma","Unresectable Basal Cell Carcinoma","Unresectable Clear Cell Renal Cell Carcinoma","Unresectable Colorectal Carcinoma","Unresectable Cutaneous Melanoma","Unresectable Mucosal Melanoma","2026-05-01",{"date":474,"type":35},"2026-05-08",{"date":395,"type":20},{"date":477,"type":20},"2029-08-31",{"name":479,"class":42},"Fred Hutchinson Cancer Center",{"id":481,"slug":4,"hasResults":11,"nctId":482,"briefTitle":483,"officialTitle":484,"acronym":4,"eligibilityCriteria":485,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":486,"targetDuration":4,"studyType":21,"phases":488,"briefSummary":489,"conditions":490,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":109,"lastUpdatePostDateStruct":491,"startDateStruct":493,"completionDateStruct":495,"leadSponsor":497,"locationsCount":335},"100535242","NCT06249282","Carfilzomib in Combination With Sotorasib for the Treatment of Patients With KRAS G12C Mutated Advanced or Metastatic Non-small Cell Lung Cancer","A Phase I Clinical Trial of Carfilzomib in Combination With Sotorasib in Patients With KRASG12C Mutated Advanced Non-Small Cell Lung Cancer","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative\n* Age: ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) ≤ 2\n* Histologically confirmed NSCLC that is metastatic or advanced. The tumor must exhibit evidence of KRASG12C mutation which is determined by either a Clinical Laboratory Improvement Act (CLIA) certified ctDNA assay or by a CLIA certified tumor tissue assay\n* Measurable disease by RECIST v1.1\n* Failed prior KRAS inhibitor\n* Fully recovered from the acute toxic effects (except alopecia) from prior anti-cancer therapy\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required during the first cycle of therapy\n* Absolute neutrophil count (ANC) ≥ 1,500\u002Fmm\\^3 (performed within 14 days prior to day 1 of protocol therapy)\n\n  * NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement\n* Hemoglobin (Hb) ≥ 9 g\u002FdL (performed within 14 days prior to day 1 of protocol therapy)\n* Platelets ≥ 100,000\u002Fmm\\^3 (performed within 14 days prior to day 1 of protocol therapy)\n\n  * NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement\n* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 14 days prior to day 1 of protocol therapy)\n* Aspartate aminotransferase (AST) ≤ 3 x ULN (or ≤ 5 x ULN in the setting of liver metastatic disease) (performed within 14 days prior to day 1 of protocol therapy)\n* Alanine aminotransferase (ALT) ≤ 5 x ULN (or ≤ 5 x ULN in the setting of liver metastatic disease) (performed within 14 days prior to day 1 of protocol therapy)\n* Creatinine clearance of ≤ 1.5 x ULN or glomerular filtration rate (GFR) ≥ 60 mL\u002Fmin\u002F1.73 m\\^2 (performed within 14 days prior to day 1 of protocol therapy)\n* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (performed within 14 days prior to day 1 of protocol therapy)\n\n  * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 120 days after the last dose of protocol therapy.\n\n  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \\> 1 year (women only)\n\nExclusion Criteria:\n\n* Chemotherapy or immunotherapy within 21 days prior to day 1 of protocol therapy\n* Radiation therapy within 14 days prior to day 1 of protocol therapy\n* KRAS inhibitor within 14 days prior to day 1 of protocol therapy\n* Investigational therapy within 28 days prior to day 1 of protocol therapy (or 5 half-lives, use whichever is shorter)\n* Inability to previously tolerate (240 mg, QD) sotorasib\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent\n* Clinically significant uncontrolled illness\n* Evidence of chronic hepatitis B virus (HBV) infection and HBV viral load detectable\n* Evidence of untreated chronic hepatitis C virus (HCV) infection. Patients with HCV infection currently on treatment are eligible if they have an undetectable HCV viral load\n* Active infection requiring antibiotics (not to be completed by day 1 of protocol therapy)\n* Known history of immunodeficiency virus (HIV) with detectable viral load\n* Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen\n* New York Heart Association (NYHA) class III or IV heart failure, myocardial infarction in the preceding 6 months, conduction abnormalities uncontrolled by medications\n* Females only: Pregnant or breastfeeding\n* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures\n* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility\u002Flogistics)",{"count":487,"type":20},15,[77],"This phase I trial tests the safety, side effects, and best dose of carfilzomib in combination with sotorasib in treating patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Carfilzomib is a drug that binds to and inhibits the activity of the protein complex that is responsible for degrading other damaged or unneeded proteins. The inhibition of this protein by carfilzomib can then cause tumor growth inhibition and cell death. Sotorasib is a drug that binds to and inhibits the activity of the KRAS G12C mutant. This may inhibit growth in KRAS G12C-expressing tumor cells. Combining carfilzomib and sotorasib may be a safe and effective treatment option for patients with KRAS G12C-mutated advanced or metastatic NSCLC.",[105,28,82,30],{"date":492,"type":35},"2026-04-03",{"date":494,"type":35},"2024-04-24",{"date":496,"type":20},"2026-11-24",{"name":419,"class":42},{"id":499,"slug":4,"hasResults":11,"nctId":500,"briefTitle":501,"officialTitle":502,"acronym":4,"eligibilityCriteria":503,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":504,"targetDuration":4,"studyType":21,"phases":506,"briefSummary":507,"conditions":508,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":509,"lastUpdatePostDateStruct":510,"startDateStruct":512,"completionDateStruct":514,"leadSponsor":516,"locationsCount":114},"100421009","NCT04762199","MRX-2843 and Osimertinib for the Treatment of Advanced EGFR Mutant Non-small Cell Lung Cancer","A Phase 1b Safety and Pharmacodynamic Study of MER Tyrosine Kinase Inhibitor, MRX-2843, in Combination With Osimertinib in Advanced EGFR Mutant Non-Small Cell Lung Cancer","Inclusion Criteria:\n\n* Patients must have histologically confirmed metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation including typical and atypical mutations in egfr exons 19 and 21\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2\n* Patients in the expansion cohort must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \\>= 20 mm (\\>= 2 cm) by chest x-ray or as \\>= 10 mm (\\>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam\n* Ability to safely swallow oral medication\n* Absolute neutrophil count \\>= 1500\u002Fmm\\^3\n* Platelet count \\>= 100,000\u002Fmm\\^3\n* Hemoglobin \\>= 8.5 g\u002FdL (must be \\> 2 weeks post-red blood cell transfusion)\n* Bilirubin =\\\u003C 1.5 x the upper limit of normal (ULN). For subjects with documented Gilbert's disease, bilirubin =\\\u003C 3.0 mg\u002FdL. For subjects with documented liver metastases, bilirubin =\\\u003C 2.5 x ULN\n* Serum creatinine =\\\u003C 1.5 x the ULN or creatinine clearance (CrCl) \\>= 50 mL\u002Fmin. For creatinine clearance estimation, the Cockcroft and Gault equation should be used\n* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\\\u003C 3 x the ULN (=\\\u003C 5 x the ULN for subjects with liver metastases)\n* The effects of MRX-2843 and osimertinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration\n* Females of childbearing potential who are sexually active with a non-sterilized male partner agree to use 2 methods of effective contraception from screening, and agree to continue using such precautions for 90 days after the final dose of study drug; cessation of birth control after this point should be discussed with a responsible physician. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause)\n* Non-sterilized males who are sexually active with a female of childbearing potential must agree to use an acceptable method of effective contraception from Day 1 and for 90 days after the final dose of study drug\n* Female subjects of childbearing potential must be nonpregnant, and have a negative pregnancy test result at screening and day 1 of cycles 1-6\n* Ability to understand and the willingness to sign a written informed consent document\n* COHORT SPECIFIC ELIGIBILITY REQUIREMENTS\n* Dose Escalation Cohort: Patients with progressive EGFR (+) NSCLC disease; previously treated or naive to EGFR-tyrosine kinase inhibitor (TKI) (previous treatment with 3rd generation EGFR-TKI including osimertinib allowed\n* Dose Expansion Cohort A (Treatment naive):\n\n  * Be treatment naive to osimertinib or any other EGFR TKI,\n  * If treated with an EGFR TKI in the adjuvant, must have discontinued treatment prior to disease recurrence and be free of recurrence for at least 12 months (+1 day) while off treatment\n* Dose Expansion Cohort B (EGFR TKI resistant):\n\n  * Have progression of disease on osimertinib, erlotinib, gefitinib or afatinib as last previous systemic treatment,\n  * If not previously treated with osimertinib, must be EGFR-T790M negative as confirmed using a standard testing platform (circulating tumor deoxyribonucleic acid \\[ctDNA\\] or tissue based testing) prior to study treatment\n* Backfill Cohort C: This cohort will be open to candidates who are not able to get into any of the dose escalation or expansion cohorts. Examples will be a patient already on osimertinib but without disease progression or an otherwise eligible patient who is unable to wait for new cohorts to open due to disease burden and symptoms.\n\nSuch patients may be enrolled into the backfill cohort if they meet the following criteria:\n\n* Patients must meet the general eligibility requirements but do not meet cohort specific requirements,\n* If currently on osimertinib, must have tolerated the standard dose of 80 mg for at least 2 cycles without any grade \\> 2 adverse events,\n* Will be treated at a dose previously established to be safe from the dose escalation cohort,\n* Will not be included in the dose limiting toxicity (DLT) or maximum tolerated dose (MTD) determination,\n* Approval by the study sponsor\n\nExclusion Criteria:\n\n* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1)\n* Patients who are receiving any other investigational agents\n* Patients with symptomatic untreated brain metastases would be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patient with treated or asymptomatic untreated brain metastasis is allowed on study\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to MRX-2843 or osimertinib\n* Patients with known diagnosis of interstitial lung disease\u002Fpneumonitis\n* Patients with corrected QT (QTc) interval prolongation \\> 500 msec (average of 3 readings), family history of congenital long QTc syndrome or torsades\n* Patients with known cardiomyopathy or decreased left ventricular ejection fraction (LVEF) \\\u003C 50%\n* Patient with known history of keratitis or symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and\u002For red eye)\n* Patients receiving any medications or substances that are inhibitors or inducers of CYP450 enzyme(s) are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Pregnant women are excluded from this study because osimertinib is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with osimertinib and MRX-2843, breastfeeding should be discontinued if the mother is treated with the study agents\n* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with osimertinib and MRX-2843. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated\n* Subject has known or suspected history of retinitis pigmentosa or known or suspected familial history of retinitis pigmentosa\n* Subject has a history of type 1 diabetes (T1D) or is considered at high risk for T1D, where high risk is defined as\n\n  * Subject has one first-degree relative (defined as parents, offspring or siblings) with T1D and A1C value \\> 6.5% or subject with two or more first-degree relatives with T1D",{"count":505,"type":20},69,[77],"This phase Ib trial evaluates the best dose and side effects of MRX-2843 when given in combination with osimertinib in treating patients with EGFR gene mutant non-small cell lung cancer that has spread to other places in the body (advanced). MRX-2843 and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.",[105,28,30,213,217],"2026-03-26",{"date":511,"type":35},"2026-03-31",{"date":513,"type":35},"2021-02-24",{"date":515,"type":20},"2026-12-27",{"name":517,"class":42},"Emory University",{"id":519,"slug":4,"hasResults":11,"nctId":520,"briefTitle":521,"officialTitle":522,"acronym":523,"eligibilityCriteria":524,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":525,"targetDuration":4,"studyType":527,"phases":4,"briefSummary":528,"conditions":529,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":546,"lastUpdatePostDateStruct":547,"startDateStruct":549,"completionDateStruct":550,"leadSponsor":552,"locationsCount":553},"100542959","NCT06349642","Immune Checkpoint Inhibitor Response in Solid Tumors Using a Live Tumor Diagnostic Platform","Observational Basket Trial to Collect Tissue to Develop and Train a Live Tumor Diagnostic Platform","ELEPHAS-04","Inclusion Criteria:\n\nSubjects must meet one of the following criteria:\n\n* Subjects suspected of or diagnosed with the following Stage IV\u002Fmetastatic or recurrent malignancies:\n\n  * Lung: Non-small Cell Lung Cancer (NSCLC)\n  * Skin: Cutaneous Malignancy, excluding Uveal Melanoma\n  * Esophageal Cancer\n  * Cervical Cancer\n  * Endometrial Cancer\n  * Colon Cancer: Mismatch repair deficient (dMMR) CRC only\n  * All solid tumors with high tumor mutation burden (TMB)\n  * All solid tumors that are microsatellite instability high (MSI-H)\n  * All mismatch repair deficient (dMMR) solid tumors\n  * Liver Cancer\n  * Any solid tumor with measurable disease that is eligible for pure ICI therapy or that the clinician plans to treat with immune checkpoint inhibitor (ICI) therapy. NOTE: This can be in the setting of a trial, compassionate use, or the use of appropriate laboratory developed tests (LDTs) that, per clinician, render the patient eligible for ICI therapy, either frontline or a later line.\n\nOR\n\n* Subjects suspected of or diagnosed with the following Stage III per provider discretion or IV\u002Fmetastatic malignancies:\n\n  * Kidney: Clear Cell Renal Cell Carcinoma (ccRCC)\n  * Bladder: Urothelial Carcinoma (UC)\n  * Any solid tumor with measurable disease that is eligible for pure ICI therapy or that the clinician plans to treat with ICI therapy. NOTE: This can be in the setting of a trial, compassionate use, or the use of appropriate LDT tests that per clinician, render the patient eligible for ICI therapy, either frontline or a later line\n\nOR\n\n* Patients who will be receiving neoadjuvant CPI for the following resectable early-stage malignancies:\n\n  * Breast Cancer: Triple negative breast cancer (TNBC)\n  * Lung: Non-small cell lung cancer (NSCLC)\n\n    * NOTE: Patients with suspected NSCLC who would be eligible for neoadjuvant checkpoint inhibitor (CPI) are eligible to enroll per provider discretion\n  * Any solid tumor that is eligible for pure ICI therapy or that the clinician plans to treat with ICI therapy. NOTE: This can be in the setting of a trial, compassionate use, or the use of appropriate LDT tests that per clinician, render the patient eligible for ICI therapy, either frontline or a later line\n* LOCALLY ADVANCED\u002FMETASTATIC PATIENTS: Measurable disease as defined per protocol NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease; Disease that is measurable by physical examination only is not eligible.\n* NEOADJUVANT PATIENTS: Subjects must be eligible based on investigator discretion to receive approved CPI therapy.\n* Subjects who are newly diagnosed or have suspected cancer must be treatment-naïve at the time of biopsy.\n* Subjects who are Stage I, II, or III and have progressed to metastatic cannot have received any anti-cancer treatment for at least 2 - 4 weeks (depending upon the washout period of prior anti-cancer treatment) prior to biopsy as per the agents used.\n* ECOG Performance Status (PS) 0, 1 or 2.\n* Negative pregnancy test done ≤7 days prior to enrollment, for persons of childbearing potential only\n* Female subjects must not be pregnant or breastfeeding and must use appropriate methods of contraception when applicable.\n* Subjects must be clinically able, at investigator discretion, and willing to undergo either:\n\n  * additional biopsy passes during their standard of care biopsy, OR\n  * a biopsy for research only, if applicable.\n  * NOTE: These additional biopsies may either be collected from the primary tumor or a metastatic site amenable to biopsies per the clinician.\n* Subjects with a known secondary cancer diagnosis are eligible to participate if participation does not interfere with systemic anti-cancer standard of care treatment for suspected primary diagnosis.\n* Provide written informed consent\n\nExclusion Criteria:\n\n* Pregnant women because this study involves a greater than minimal risk procedure (biopsy)\n* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety for the biopsy\n* Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy\n\n  * NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial\n* Uncontrolled intercurrent illness including, but not limited to:\n\n  * ongoing or active infection\n  * psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Subjects who are enrolled or plan to be enrolled in a blinded cancer therapeutic treatment trial",{"count":526,"type":20},324,"OBSERVATIONAL","This study is being done to collect tissue samples to test how accurately a tumor response platform, Elephas, can predict clinical response across multiple types of immunotherapies, chemoimmunotherapy and tumor types.",[530,531,184,459,460,185,532,533,28,534,57,535,536,537,538,197,208,60,236,539,540,541,542,543,267,544,545],"Early Stage Triple-Negative Breast Carcinoma","Metastatic Bladder Urothelial Carcinoma","Metastatic Esophageal Carcinoma","Metastatic Liver Carcinoma","Metastatic Malignant Skin Neoplasm","Resectable Lung Non-Small Cell Carcinoma","Early Stage Lung Non-Small Cell Carcinoma","Resectable Malignant Solid Neoplasm","Resectable Triple-Negative Breast Carcinoma","Recurrent Cervical Carcinoma","Recurrent Colorectal Carcinoma","Recurrent Endometrial Carcinoma","Recurrent Esophageal Carcinoma","Recurrent Liver Carcinoma","Recurrent Malignant Skin Neoplasm","Recurrent Malignant Solid Neoplasm","2026-03-11",{"date":548,"type":35},"2026-03-12",{"date":494,"type":35},{"date":551,"type":20},"2027-05",{"name":245,"class":42},3,{"id":555,"slug":4,"hasResults":11,"nctId":556,"briefTitle":557,"officialTitle":558,"acronym":4,"eligibilityCriteria":559,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":560,"targetDuration":4,"studyType":21,"phases":561,"briefSummary":562,"conditions":563,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":577,"lastUpdatePostDateStruct":578,"startDateStruct":579,"completionDateStruct":581,"leadSponsor":583,"locationsCount":114},"100446805","NCT05098210","Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma, Hormone Receptor Positive HER2 Negative Metastatic Refractory Breast Cancer or Stage III-IV Non-Small Cell Lung Cancer","PNV21-001: A Phase I Study of a Personalized Multi-Peptide Neo-Antigen Vaccine in Breast Cancer, PD1\u002FPD-L1 Inhibitor-Refractory Melanoma, and Pretreated Non-Small Cell Lung Cancer","Inclusion Criteria:\n\n* Female and\u002For male patients age \\>= 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2\n* Patients must have at least 1 lesion (or aggregate lesions) to obtain tumor tissue for resection of \\>= 1 cm or \\>= 4 core biopsies acceptable. Amenable to image (CT, ultrasound \\[U\u002FS\\], or magnetic resonance imaging \\[MRI\\]) guided biopsy for tissue collection necessary for neoantigen identification. Either primary or metastatic sites are options for tissue collection\n* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as \\>= 10 mm, unless lymph node in which case short axis must be \\>= 15 mm. Baseline imaging (for example diagnostic CT chest\u002Fabdomen\u002Fpelvis, PET CT scan and imaging of the affected extremity as appropriate), brain imaging (MRI or CT scan) must be obtained within 45 days of prior to start of first planned vaccine dose infusion. MRI can be substituted for CT in patients unable to have CT contrast\n* Serum creatine \\\u003C 1.5 mg\u002FdL or estimated glomerular filtration rate (eGFR) \\> 60 mL\u002Fmin\n* Total bilirubin (tBili) \\\u003C 1.5 x upper limit of normal (ULN) and an aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) \\\u003C 2.5 x ULN and \\\u003C 5 x ULN for subjects with documented liver metastasis. Patients with suspected Gilbert syndrome may be included if tBili \\> 3 but no other evidence of hepatic dysfunction\n* =\\\u003C grade 1 dyspnea and arterial oxygen saturation (SaO2) \\>= 92% on ambient air. If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, patients with forced expiratory volume in 1 second (FEVI) \\>= 70% of predicted and carbon monoxide diffusing capability (DLCO) (corrected) of \\>= 60% of predicted will be eligible\n* Patients with active interstitial lung disease (ILD)\u002Fpneumonitis or a history of ILD\u002Fpneumonitis requiring treatment with systemic steroids will be excluded\n* Patients 60 years of age or older are required to have left ventricular ejection fraction (LVEF) evaluation performed within 60 days prior to enrollment. LVEF may be established with echocardiogram or MUGA scan, and left ejection fraction must be \\>= 50%. Cardiac evaluation for other patients is at the discretion of the treating physician\n* Subjects with a history of myocarditis or congestive heart failure (as defined by New York Heart Association functional classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry will be excluded\n* Absolute neutrophil count (ANC) \\> 1000 cells\u002Fmm\\^3\n* Hemoglobin \\>= 9 mg\u002FdL\n* Platelet count \\>= 50,000\u002FuL\n* Toxicity from prior therapy must be recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5 grade 2 or less\n* Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures\n* Capable of understanding and providing a written informed consent\n* The effects of neoantigen vaccination on the developing human fetus are unknown. For this reason, patients who are having sex that can lead to pregnancy must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) for the duration of study participation. Should a woman become pregnant while participating in the study, she should inform her study doctor immediately and will not receive any more study treatment\n* MELANOMA SPECIFIC: Tissue confirmation of melanoma: Histologically confirmed metastatic (recurrent or de novo stage IV) or unresectable locally advanced (stage IIIC or IIID) cutaneous, acral, conjunctival or mucosal melanoma, as defined by the American Joint Committee on Cancer (AJCC) v8.0. Confirmation of diagnosis must be or have been performed by internal pathology review of archival, initial or subsequent biopsy or other pathologic material at Fred Hutchinson Cancer Center (FHCC)\u002FUniversity of Washington Medical Center (UWMC)\n* MELANOMA SPECIFIC: Patients must have received stage specific standard of care therapy per National Comprehensive Cancer Network (NCCN) guidelines and have persistent\u002Frecurrent disease after at least one line of therapy prior to enrollment on the study\n* MELANOMA SPECIFIC: Known BRAF mutational status\n* MELANOMA SPECIFIC: History of detectable disease during\u002Fafter treatment with a PD-1 or PD-L1 inhibitor, as defined by the Society of Immunotherapy of Cancer's definition of primary or secondary resistance (Kluger and others \\[et al.\\], 2020):\n\n  * Drug exposure \\>= 6 weeks and best response progressive disease (PD) or stable disease (SD) \\\u003C 6 months or\n  * Drug exposure \\>= 6 months and best response complete response (CR), partial response (PR), or SD \\> 6 months\n* MELANOMA SPECIFIC: A confirmatory scan performed at least 4 weeks after disease persistence\u002Fprogression is required but this requirement can be waived if the judgement of the treating clinician is that the patient would be at risk of rapid or symptomatic progression in that interval. This confirmatory scan can occur during production of the vaccine after enrollment\n* BREAST CANCER SPECIFIC: Tissue confirmation of stage IV (recurrent or de novo metastatic) hormone receptor (HR) positive, HER2 negative breast cancer:\n\n  * Hormone receptor (HR) positive breast cancer as defined by either one, or both of the following criteria:\n\n    * Estrogen receptor (ER) positive disease defined as follows documented by a local laboratory: 1-100% positive stained cells based on de novo tumor biopsy\n    * Progesterone receptor (PR) positive disease defined as follows documented by a local laboratory: 1-100% positive stained cells based on de novo tumor biopsy\n  * Human epidermal growth factor receptor 2 (HER2) negative breast cancer (per American Society of Clinical Oncology \\[ASCO\\]\u002FCollege of American Pathologists \\[CAP\\] guideline update, 2018) as documented by a local laboratory with HER2-negativity defined as:\n\n    * Immunohistochemistry score 0\u002F1+ or 2+ and \u002F or\n    * Negative by in situ hybridization (fluorescence in situ hybridization \\[FISH\\]\u002Fchromogenic in situ hybridization \\[CISH\\]\u002Fsilver-enhanced in situ hybridization \\[SISH\\]) per ASCO\u002FCAP guideline update, 2018\n  * Confirmation of diagnosis must be or have been performed by internal pathology review of archival, initial or subsequent biopsy or other pathologic material at FHCC\u002FUWMC\n* BREAST CANCER SPECIFIC: Patients must have received at least one line of systemic therapy in the metastatic setting prior to enrollment on the study and have progressive\u002Fpersistent disease after\n* NON-SMALL CELL LUNG CANCER SPECIFIC: Tissue confirmation of stage III unresectable or stage IV (recurrent or de novo metastatic) non-small cell lung cancer (NSCLC):\n\n  * Genetic testing must have been performed for targetable driver mutations, including EGFR, ROS1, Alk, KRAS, BRAF\n  * Confirmation of diagnosis must be or have been performed by internal pathology review of archival, initial or subsequent biopsy or other pathologic material at FHCC\u002FUWMC\n* NON-SMALL CELL LUNG CANCER SPECIFIC: Patients must have received at least one line of systemic therapy in the metastatic or stage II or III setting including a PD-1 or PD-L1 inhibitor prior to enrollment on the study and have progressive or recurrent disease after\n* NON-SMALL CELL LUNG CANCER SPECIFIC: For patients who have received neoadjuvant, adjuvant, and\u002For consolidation anti-PD-1 or anti-PD-L1 for stage II or III disease, they must have experienced disease progression in less than or equal to 365 days from initiation (cycle 1 day 1) of anti-PD-1 or anti-PD-L1 therapy for this to count as the systemic therapy for advanced disease. Patients experiencing progression more than 365 days from initiation (cycle 1 day 1) of anti-PD-1 or anti-PD-L1 therapy will not be considered as having received one line of systemic therapy. These patients must have received an anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease\n\nExclusion Criteria:\n\n* Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 5 months after the last dose of investigational product\n* Any history of an immune-related grade 4 adverse event attributed to prior cancer immunotherapy CIT (other than endocrinopathy managed with replacement therapy or asymptomatic elevation of serum amylase or lipase)\n* Any history of an immune-related grade 3 adverse event attributed to prior CIT that required permanent discontinuation of PD-1 inhibitor therapy\n* Immune-related adverse events related to prior CIT (other than endocrinopathy managed with replacement therapy or stable vitiligo) that have not resolved to baseline. Patients treated with corticosteroids for immune-related adverse events must demonstrate absence of related symptoms or signs for \\>= 4 weeks following discontinuation of corticosteroids\n* Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated \\> 4 weeks prior to enrollment. Patients should be recovered from the effects of radiation\n* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX®) are allowed\n* Patients with known symptomatic brain metastases. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable for \\>= 1 months (confirmed by magnetic resonance imaging \\[MRI\\])\n* Patients with rapidly progressing disease, symptomatic visceral disease, or patients who are expected to have rapidly progressive disease over the course of several months despite bridging therapy approved by the protocol\n* Known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T-negative severe combined immunodeficiency \\[SCID\\]) or combined T- and B-cell immunodeficiencies (e.g., T- and B-negative SCID, Wiskott-Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency)\n* Prior allogeneic bone marrow transplantation or prior solid organ transplantation\n* Known positive test for HIV infection\n* Patients with active infection causing fever (temperature \\> 38.1 degrees Celsius \\[C\\]) or subjects with unexplained fever (temperature \\> 38.1 degrees C) may not receive the investigational product unless the fever is =\\\u003C 38.1 for 5 days prior to start\n* Active uncontrolled infection: individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have, per standard practice, hepatitis well-controlled on medication (e.g., AST and ALT \\\u003C 5 x ULN) can be included\n* History of autoimmune disease that has not been controlled with treatment in the last 12 months, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions: Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., no psoriatic arthritis) may be eligible\n* Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone \\> 10 mg\u002Fday or equivalent, cyclophosphamide, azathioprine, methotrexate, thalidomide, and TNF-alpha antagonists) within 2 weeks prior screening. The use of topical, eye drops, local injections, or inhaled corticosteroids (e.g. fluticasone for chronic obstructive pulmonary disease) is allowed. The use of oral mineralocorticoids (e.g. fludrocortisone for patients with orthostatic hypotension) is allowed. Physiologic doses of corticosteroids for adrenal insufficiency are allowed. Low dose corticosteroids for a short duration \\[5 mg once daily (QD) prednisone for 2 weeks\\] as symptomatic treatment and upon with discussion with the investigator is allowed. Note: Patients with adrenal insufficiency may take 10 mg of prednisone or equivalent daily\n* Subjects should have an international normalized ratio (INR) or activated partial thromboplastin time (aPTT) =\\\u003C 1.5 X ULN unless the subject is receiving anticoagulant therapy. Subjects on anticoagulant therapy should have a prothrombin time (PT) or partial thromboplastin time (PTT) within therapeutic range of intended use and no history of severe hemorrhage. Antiplatelet agents (eg, aspirin, clopidogrel, etc.) are not considered anticoagulants for the purposes of this study (i.e., they are allowed)\n* Other medical, social, or psychiatric factor that interferes with medical appropriateness and\u002For ability to comply with study, as determined by the principal investigator (PI)\n* Participants of childbearing potential must have a negative serum pregnancy test within 14 days prior to enrollment. Childbearing potential is defined as women who have not been surgically sterilized and who are not post-menopausal (free of menses for at least 1 year)\n* Female patients who are lactating or intend to breastfeed during the duration of the study\n* Patients who have received a live vaccine within 30 days prior to enrollment\n* Patients with any underlying medical condition for which, in the investigator's opinion, participation would not be in the best interest of the participant (e.g.- compromises the health of the subject) or that could prevent, limit or confound protocol assessments\n* MELANOMA SPECIFIC: Uveal or choroidal melanoma. This entity is excluded due to the absence of abundant mutations\n* BREAST SPECIFIC: Patients with symptomatic disease including patients with symptomatic lung metastases, bone marrow replacement with associated cytopenia, or significant liver metastases with associated liver dysfunction\n* NON-SMALL CELL LUNG CANCER SPECIFIC: Activating mutations in EGFR or genetic alterations in ROS1 or Alk, as these mutations are associated with lower mutation burden and non-response to immune therapies",{"count":7,"type":20},[77],"This phase I trial studies the safety of personalized neo-antigen peptide vaccine in treating patients with stage IIIC-IV melanoma, hormone receptor positive HER2 negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or does not respond to treatment (refractory) or stage III-IV non-small cell lung cancer. Personalized neo-antigen peptide vaccine is a product that combines multiple patient specific neo-antigens. Given personalized neo-antigen peptide vaccine together with Th1 polarizing adjuvant poly ICLC may induce a polyclonal, poly-epitope, cytolytic T cell immunity against the patient's tumor.",[26,158,564,565,566,567,461,568,569,28,57,463,570,571,572,573,574,267,575,82,30,576,470,226,471],"Locally Advanced Cutaneous Melanoma","Locally Advanced Mucosal Melanoma","Metastatic Acral Melanoma","Metastatic Conjunctival Melanoma","Metastatic HER2-Negative Breast Carcinoma","Metastatic Hormone Receptor-Positive Breast Carcinoma","Pathologic Stage IIIC Cutaneous Melanoma AJCC v8","Pathologic Stage IIID Cutaneous Melanoma AJCC v8","Recurrent Cutaneous Melanoma","Recurrent HER2-Negative Breast Carcinoma","Recurrent Hormone Receptor-Positive Breast Carcinoma","Recurrent Mucosal Melanoma","Unresectable Acral Melanoma","2026-03-10",{"date":548,"type":35},{"date":580,"type":35},"2022-06-09",{"date":582,"type":20},"2028-11-01",{"name":479,"class":42},{"id":585,"slug":4,"hasResults":11,"nctId":586,"briefTitle":587,"officialTitle":588,"acronym":4,"eligibilityCriteria":589,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":590,"targetDuration":4,"studyType":21,"phases":591,"briefSummary":592,"conditions":593,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":594,"lastUpdatePostDateStruct":595,"startDateStruct":597,"completionDateStruct":599,"leadSponsor":601,"locationsCount":114},"100563473","NCT06616623","Vismodegib and Atezolizumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer","A Phase Ib Study of Vismodegib and Atezolizumab in Patients With Advanced Non-Small Cell Lung Cancer (ML43922)","Inclusion Criteria:\n\n* Age ≥ 18 years\n* Confirmed recurrent or metastatic non-small cell carcinoma of the lung of any histology without curative options\n* Measurable disease based on RECIST v1.1\n* Patients must have received standard of care chemotherapy and\u002For immunotherapy. No limits to prior lines of therapy. Prior PD-1 and\u002For PD-L1 directed therapies are permitted\n* Patients with adenocarcinoma and known actionable mutations with Food and Drug Administration (FDA) approved treatment options must have received all approved and standard of care treatment options (i.e. osimertinib for epidermal growth factor receptor (EGFR), alectinib for anaplastic lymphoma kinase (ALK), etc.). Mutational testing is not required for patients with squamous cell non-small cell lung carcinoma\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2\n* Absolute neutrophil count (ANC) ≥ 1,500 \u002FmcL without granulocyte colony-stimulating factor support\n* Platelet count ≥ 100,000 \u002FuL without transfusion\n* Hemoglobin ≥ 90 g\u002FL (9 g\u002FdL) patients may be transfused to meet this criterion\n* Measured or calculated creatinine clearance (calculated using the Cockcroft-Gault formula) ≥ 60 mL\u002Fmin for subject with creatinine levels ≤ 1.5 x institutional upper limit of normal (ULN)\n* Serum total bilirubin ≤ 1.5 x ULN with the following exception:\n\n  * Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN\n* Direct bilirubin ≤ ULN for subjects with total bilirubin levels \\> 1.5 ULN\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 2.5 x ULN with the following exceptions:\n\n  * Patients with documented liver metastases: AST and ALT ≤ 5 x ULN\n  * Both values must be in the specified range\n* Alkaline phosphatase (ALP) ≤ 2.5 x ULN with the following exceptions:\n\n  * Patients with documented liver or bone metastases: ALP ≤ 5 x ULN\n* Albumin ≥ 2.5 g\u002FdL\n* International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy\n\n  * As long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants\n* Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy\n\n  * As long as PT or PTT is within therapeutic range of intended use of anticoagulants\n* Anticipated life expectancy of ≥ 3 months\n* Willing to comply with study procedures\n* Female subject of childbearing potential will have a serum pregnancy test at screening. Urine pregnancy tests will be performed at specified subsequent visits. If a urine pregnancy test is positive, it must be confirmed by a serum pregnancy test\n* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:\n\n  * Women must remain abstinent or use contraceptive methods with a failure rate of \\< 1% per year during the treatment period and for 5 months after the final dose of atezolizumab and 24 months after the final dose of vismodegib. Women must refrain from donating eggs during this same period\n  * A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and\u002For uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirement\n  * Examples of contraceptive methods with a failure rate of \\< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices\n  * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception\n* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, for 5 months from last atezolizumab dose and 24 months after the final dose of vismodegib, as defined below:\n\n  * With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and, for 5 months from last atezolizumab dose and 24 months after the final dose of vismodegib to avoid exposing the embryo. Men must refrain from donating sperm during this same period\n  * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure\n* Be willing and able to understand and sign the written informed consent document\n* Availability of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block. A recently obtained archival FFPE tumor tissue block (if an FFPE tissue block cannot be provided, 15 unstained slides (10 minimum) will be acceptable) from a primary or metastatic tumor resection or biopsy can be provided if it was obtained within 1 year of trial screening\n* Be willing to provide tissue from an on-treatment fine needle aspiration (FNA) or core biopsy of a tumor lesion. Subjects must consent to on-treatment biopsy prior to initiation of clinical trial, however subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may still continue on study\n* Negative HIV test at screening with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count \\> 200\u002FuL, and have an undetectable viral load\n* Negative total hepatitis B core antibody (HBcAb) test at screening. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening\n\n  * The HCV RNA test must be performed for patients who have a positive HCV antibody test\n\nExclusion Criteria:\n\n* Active autoimmune disease requiring treatment or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions:\n\n  * Patients with a history of autoimmune-related hypothyroidism who are stable on thyroid-replacement hormone are eligible for the study\n  * Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study\n  * Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:\n\n    * Rash must cover ≤ 10% of body surface area\n    * Disease is well controlled at baseline and requires only low-potency topical corticosteroids\n    * No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months\n* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment\n* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at doses \\> 10 mg prednisone or equivalent or other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment\n* Cirrhosis (Child-Pugh B or worse) or cirrhosis with history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis\n* Has symptomatic central nervous system (CNS) metastases and\u002For carcinomatous meningitis. Subjects with asymptomatic CNS lesions will be eligible if considered appropriate by the treating physician. Subjects with previously treated brain metastases may participate provided they have had a stable neurological status for at least 2 weeks after completion of definitive therapy\n\n  * Asymptomatic patients with treated CNS lesions are eligible, provided that all of the following criteria are met:\n\n    * Measurable disease, per RECIST v1.1, must be present outside the CNS\n    * The patient has no history of intracranial hemorrhage or spinal cord hemorrhage\n    * The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment\n    * The patient has no ongoing requirement for corticosteroids as therapy for CNS disease\n    * If the patient is receiving anti-convulsant therapy, the dose is considered stable\n* Pregnancy or breastfeeding or intention of becoming pregnant during study treatment or within 5 months for atezolizumab or within 24 months after the final dose of vismodegib.\n\n  * Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator\n* Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications\n* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted\n* Known active tuberculosis (specific testing is only needed if clinically indicated)\n* Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina\n* Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could impact patient safety\n* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study\n* Prior allogeneic stem cell or solid organ transplantation\n* Live, attenuated vaccines (e.g., FluMist®) are prohibited within 4 weeks prior to initiation of study treatment, during treatment with atezolizumab, and for 5 months after the last dose of atezolizumab\n* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \\[IL-2\\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment\n* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins\n* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation\n* Any patient who experience unacceptable toxicity on prior checkpoint inhibitor therapy:\n\n  * ≥ grade 3 adverse event (AE) related to checkpoint inhibitor\n  * ≥ grade 2 immune-related AE associated with checkpoint inhibitor\n  * CNS, ocular or cardiac AE of any grade related to checkpoint inhibitor\n\n    * NOTE: Patients with a prior endocrine AE are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic",{"count":427,"type":20},[77],"This phase Ib trial tests the safety, side effects, and best dose of the combination of vismodegib and atezolizumab in treating patients with non-small cell lung cancer (NSCLC) that has come back after a period of improvement (recurrent) or has spread from where it first started (primary site) to other places in the body (metastatic). Vismodegib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving a combination of vismodegib and atezolizumab may be safe, tolerable and\u002For effective than either drug alone in treating patients with recurrent or metastatic NSCLC.",[28,267,30],"2026-02-24",{"date":596,"type":35},"2026-02-27",{"date":598,"type":35},"2024-12-31",{"date":600,"type":20},"2027-12-01",{"name":602,"class":42},"Dwight Owen",{"id":604,"slug":4,"hasResults":11,"nctId":605,"briefTitle":606,"officialTitle":607,"acronym":4,"eligibilityCriteria":608,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":609,"targetDuration":4,"studyType":21,"phases":611,"briefSummary":612,"conditions":613,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":614,"lastUpdatePostDateStruct":615,"startDateStruct":617,"completionDateStruct":619,"leadSponsor":621,"locationsCount":335},"100572284","NCT06731270","Diclofenac for the Treatment of Patients With Metastatic Non-small Cell Lung Cancer on Single Agent Immunotherapy","Phase II Study of Diclofenac Salvage in Patients Metastatic Non-Small Cell Lung Cancer With Early Signs of Progression on Single Agent PD(L)-1 Blockade","Inclusion Criteria:\n\n* Capable of signing informed consent\n* Age ≥ 18 years at time of study entry\n* Stage III or IV pathologically proven NSCLC with advanced or metastatic disease, currently on treatment with an Food and Drug Administration (FDA) approved single agent monoclonal antibody inhibiting the PD(L)-1 pathway (pembrolizumab, atezolizumab, nivolumab, or cemiplimab) for a minimum of 12 weeks\n\n  * May include frontline single agent immune checkpoint inhibitors (ICI), maintenance single agent ICI after chemo-ICI, or subsequent line therapy\n* Radiographic evidence of clinical progression as determined by the treating physician, not warranting immediate change of therapy. Progressive disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria is not required. This can include mixed response, will need at least one growing lesion. Exposure to PD1 inhibitor for at least 12 weeks will minimize the risk of pseudo-progression\n* Eastern Cooperative Oncology Group (ECOG) performance status 0-2\n* Life expectancy of ≥ 26 weeks\n* Absolute neutrophil count (ANC) ≥ 1,000 cell\u002Fmm\\^3\n* Platelets ≥ 100,000 cells\u002Fmm\\^3\n* Hemoglobin ≥ 8 gm\u002FdL\n* Creatinine clearance ≥ 45 ml\u002Fml\n* Bilirubin ≤ 1.5 x institutional upper limit of normal\n\n  * Bilirubin must be ≤ 3 x institutional upper limit of normal in patients with documented Gilbert's syndrome\n* Serum glutamic oxaloacetic transaminase (SGOT) \u002F serum gluatmic pyruvic transaminase (SGPT) ≤ 2.5 x institutional upper limit of normal\n* Ability to take oral medications\n* Willingness and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up\n\nExclusion Criteria:\n\n* Concurrent enrollment in another clinical study, unless it is non-therapeutic\n* Prophylactic or therapeutic anticoagulation therapy including but not limited to: warfarin, heparin, low molecular weight heparin, or direct oral anticoagulants, including: dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa), and betrixaban (Bevyxxa)\n* Treatment within the previous 6 weeks or planned initiation of bevacizumab\n* Abnormal markers of coagulation as measured by international normalized ratio (INR) \\> 2\n* Contraindication for NSAID therapy including: chronic aspirin therapy for coronary artery disease (CAD), cerebrovascular accident (CVA), or other indication, uncontrolled gastrointestinal ulcerative disease, known bleeding diathesis, known allergy or hypersensitivity to NSAIDS, advanced renal disease, uncontrolled hypertension, known seizure disorder or others\n* Female of childbearing potential unwilling or unable to use 2 methods of contraception, detailed in protocol\n* Uncontrolled intercurrent illness\n* History of another primary malignancy with exceptions noted in protocol\n* History of active primary immunodeficiency or active infection including tuberculosis, hepatitis B, hepatitis C\n* Current or prior use of immunosuppressive medication within 14 days before the first dose of diclofenac. There are exceptions to this criterion\n* Receipt of live attenuated vaccine within 30 days prior to the first dose of study medications\n* Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements",{"count":610,"type":20},20,[78],"This phase II trial tests how well diclofenac works in treating patients non-small cell lung cancer (NSCLC) that may have spread from where it first started (primary site) to other places in the body (metastatic) on single agent immunotherapy. Diclofenac, a type of non-steroidal anti-inflammatory (NSAID), blocks the body's production of a substance that causes inflammation and may decrease tumor growth and improve the effectiveness of immunotherapy. Immunotherapy with pembrolizumab, atezolizumab, nivolumab or cemiplimab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving diclofenac may kill more tumor cells in patients with metastatic NSCLC on single agent immunotherapy.",[105,28,82,30],"2026-02-10",{"date":616,"type":35},"2026-02-12",{"date":618,"type":35},"2025-04-09",{"date":620,"type":20},"2028-01-01",{"name":517,"class":42},{"id":623,"slug":4,"hasResults":11,"nctId":624,"briefTitle":625,"officialTitle":626,"acronym":4,"eligibilityCriteria":627,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":628,"targetDuration":4,"studyType":21,"phases":629,"briefSummary":630,"conditions":631,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":632,"lastUpdatePostDateStruct":633,"startDateStruct":635,"completionDateStruct":637,"leadSponsor":639,"locationsCount":114},"100457262","NCT05234307","PBF-1129 and Nivolumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer","A Phase Ib Trial of PBF-1129 and Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer","Inclusion Criteria:\n\n* Age \\>= 18 years\n* Confirmed recurrent or metastatic non-small cell carcinoma of the lung of any histology without curative options\n* Measurable disease based on RECIST 1.1\n* Patients must have received standard of care chemotherapy and immunotherapy. No limits to prior lines of therapy. Prior PD-1 and\u002For PD-L1 directed therapies are required. Prior CTLA4 therapy is permitted. Patients may have received no more than 3 prior lines of therapy in the metastatic setting (excluding targeted therapies)\n* Patients with known actionable mutations with Food and Drug Administration (FDA)-approved treatment options must have received all approved and standard of care treatment options (ie osimertinib for EGFR, alectinib for ALK, etc)\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1\n* Absolute neutrophil count (ANC) \\>= 1,500 \u002FmcL\n* Platelets \\>= 100,000 \u002F mcL\n* Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate \\[GFR\\] can also be used in place of creatinine or creatinine clearance \\[CrCl\\]) =\\\u003C 1.5 X upper limit of normal (ULN) OR \\>= 60 mL\u002Fmin for subject with creatinine levels \\> 1.5 X institutional ULN\n* Serum total bilirubin =\\\u003C 1.5 X ULN OR direct bilirubin =\\\u003C ULN for subjects with total bilirubin levels \\> 1.5 ULN\n* AAspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\\u003C 3 X ULN OR =\\\u003C 5 X ULN for subjects with liver metastases\n* Albumin \\>= 2.5 mg\u002FdL\n* International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) =\\\u003C 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants =\\\u003C 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants\n* Anticipated life expectancy of \\>= 3 months\n* Willing to comply with study procedures\n* Must be able to swallow pills\n* Female subjects of childbearing potential must be willing to use an adequate method of contraception\n* For female patients of childbearing potential, a negative serum pregnancy test within 7 days prior to first dose of protocol therapy is required\n* Be willing and able to understand and sign the written informed consent document\n* Availability of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block. A recently obtained archival FFPE tumor tissue block (if an FFPE tissue block cannot be provided, 15 unstained slides (10 minimum) will be acceptable) from a primary or metastatic tumor resection or biopsy can be provided if it was obtained within 1 year of trial screening. Patients with archival tissue that does not meet this criteria may still be eligible in the dose escalation cohort only upon approval from PI.\n* For patients in dose expansion cohort: Be willing to provide tissue from a pre-treatment and on-treatment fin needle aspirate (FNA) or core biopsy of a tumor lesion. Subjects must consent to pre-treatment and on-treatment biopsy prior to initiation of clinical trial, however subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may still continue on study\n* Be willing to provide peripheral blood samples for correlative studies\n\nExclusion Criteria:\n\n* Has active autoimmune disease, including myasthenic syndrome, which has required systemic treatment in the past 12 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided that disease is well controlled at baseline and requires only topical corticosteroids.\n* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at a dose \\> 10 mg prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment\n* Known active chronic infections - human immunodeficiency virus (HIV)\u002Facquired immunodeficiency syndrome (AIDS), known active (ie with detectable polymerase chain reaction \\[PCR\\]) Hepatitis B or C\n* Cirrhosis (Child-Pugh B or worse) or cirrhosis with history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis\n* Symptomatic central nervous system (CNS) metastases. Patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, on stable dose of steroids after cranial irradiation with maximum of 10 mg prednisone equivalent. Treatment (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) must be completed at least 2 weeks prior to study entry, or after surgical resection performed at least 28 days prior to treatment initiation. Patients with asymptomatic lesions will be eligible if considered appropriate by the treating physician.\n* Pregnancy or breastfeeding\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator\n* Any of the following cardiac criteria:\n\n  * Mean resting corrected QT interval (corrected QT \\[QTc\\] using Fredericia's formula \\[QTcF\\]) \\> 470 msec (Fridericia's Criteria for Corrected QT interval \\[QTc\\] Calculation: Fridericia's formula QTcF = (QT\u002FRR0.33). RR is the time from the interval of 1 QRS complex to the next measured in seconds and is commonly calculated as (60\u002Fheart rate \\[HR\\])\n  * Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block\n* Any patient who experience unacceptable toxicity on prior checkpoint inhibitor therapy:\n\n  * \\>= grade 3 adverse event (AE) related to checkpoint inhibitor with the exception of grade 3 pneumonitis that has resolved to grade 1 at time of study entry.\n  * Ongoing \\>= grade 2 immune-related AE associated with checkpoint inhibitor with the exception of endocrine toxicities as detailed below\n  * CNS, ocular or cardiac AE of any grade related to checkpoint inhibitor\n  * NOTE: Patients with a prior endocrine AE are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic",{"count":343,"type":20},[77],"This phase I trial studies the side effects and best dose of PBF-1129 in combination with nivolumab in treating patients with non-small cell lung cancer that has come back (recurrent) or spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as PBF-1129 and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.",[28,267,30,213,217],"2026-02-04",{"date":634,"type":35},"2026-02-06",{"date":636,"type":35},"2022-11-21",{"date":638,"type":20},"2026-12-31",{"name":602,"class":42},{"id":641,"slug":4,"hasResults":11,"nctId":642,"briefTitle":643,"officialTitle":644,"acronym":4,"eligibilityCriteria":645,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":646,"targetDuration":4,"studyType":527,"phases":4,"briefSummary":648,"conditions":649,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":650,"lastUpdatePostDateStruct":651,"startDateStruct":652,"completionDateStruct":654,"leadSponsor":656,"locationsCount":114},"100552416","NCT06472804","Insomnia in Patients With Metastatic Lung Cancer","Insomnia in Patients With Metastatic Non Small Cell Lung Cancer","Inclusion Criteria:\n\n* Have a diagnosis of metastatic non small cell lung cancer\n\n  * Undergoing 1st, 2nd or 3rd line of treatment or are in maintenance therapy\n  * Older than 18 years old at the time of diagnosis\n\nExclusion Criteria:\n\n* Subjects will be excluded if they are considered to have advanced terminal cancer, severe depression or other psychiatric disorder or a sleep disorder other than insomnia (sleep apnea, restless leg syndrome, sleep related disorder of breathing), regular use of psychotropic medication other than hypnotics (eg antidepressants) per chart review",{"count":647,"type":20},60,"This study evaluates how common insomnia (difficulties with sleep) is in patients with lung cancer that has spread from where it first started (primary site) to other places in the body.",[28,30],"2026-02-03",{"date":632,"type":35},{"date":653,"type":35},"2019-06-19",{"date":655,"type":20},"2027-06",{"name":245,"class":42},{"id":658,"slug":4,"hasResults":11,"nctId":659,"briefTitle":660,"officialTitle":661,"acronym":4,"eligibilityCriteria":662,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":663,"targetDuration":4,"studyType":21,"phases":665,"briefSummary":667,"conditions":668,"keywords":669,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":671,"lastUpdatePostDateStruct":672,"startDateStruct":674,"completionDateStruct":676,"leadSponsor":678,"locationsCount":114},"100374167","NCT04151940","PET\u002FCT Changes During Chemoimmunotherapy and Radiation Therapy in Patients With Stage IV Non-small Cell Lung Cancer","An Interventional Study of PET\u002FCT Changes During Chemoimmunotherapy and Radiation Therapy for Patients With Metastatic NSCLC (PET Bright)","Inclusion Criteria:\n\n* Histologically-confirmed or cytologically-confirmed metastatic NSCLC in patients who have not received chemotherapy or immunotherapy for their advanced disease (stage IV or recurrent, using the American Joint Committee on Cancer \\[AJCC\\]\u002FUnion for International Cancer Control \\[UICC\\] 8th edition for staging)\n* Evidence of stage IV disease on imaging by CT, PET\u002FCT, or magnetic resonance imaging (MRI)\n* Plan to treat with a platinum doublet with a PD1 or PDL1 inhibitor\n* Adjuvant chemotherapy or concurrent chemoradiation for early stage disease does not count as prior therapy unless subject progressed within 6 months of completion of regimen.\n* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, at treating physician's discretion\n* Subjects must be ≥ 18 years of age\n* Patients with known activating mutations in EGFR, BRAF or known translocation in ALK or ROS-1 are eligible provided they have progressed on or were intolerant to Food and Drug Administration (FDA) approved targeted therapy\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2\n* Creatinine =\\\u003C 2 mg\u002FdL or creatinine clearance \\> 50 mL\u002Fmin\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\\u003C 5x institutional upper limit of normal\n* Total bilirubin =\\\u003C 1.5 mg\u002FdL\n* Absolute neutrophil count (ANC) \\>= 1.5 x 10\\^9\u002FL (\\>= 1500 per mm\\^3)\n* Platelet count \\>= 100 x 10\\^9\u002FL (\\>=100,000 per mm\\^3)\n* Capability to understand and comply with the protocol requirements and signed informed consent documents\n\nExclusion Criteria:\n\n* Any known additional malignancy (with exception of non-melanoma skin cancer, in-situ breast cancer, low risk prostate cancer, or a malignancy diagnosed \\>= 3 years prior to the current NSCLC diagnosis and with no evidence of requiring active treatment)\n* Had prior treatment with an anti-PD-1, or PD-L1 or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms\n* Has any serious or uncontrolled active infection that could create false positives on a PET\u002FCT scan, in the opinion of the treating investigator\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator\n* Has an active autoimmune disease currently requiring systemic treatment (e.g. disease modifying agents, corticosteroids or immunosuppressive drugs)\n\n  \\*\\*Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment\n* Has known, active, and symptomatic central nervous system (CNS) metastases and\u002For carcinomatous meningitis\n\n  * Patients with stable or previously treated brain metastases are eligible as long as they are not receiving more than 10 mg of prednisone, or equivalent, per day",{"count":664,"type":20},80,[666],"NA","This study investigates the changes in positron emission tomography (PET)\u002Fcomputed tomography (CT) imaging scans during chemoimmunotherapy and radiation therapy treatment in patients with stage IV non-small cell lung cancer. Analyzing changes in PET\u002FCT imaging scans may help doctors assess and predict patterns of cancer response to chemoimmunotherapy and radiation therapy.",[28,267,30],[670],"Lung","2026-01-12",{"date":673,"type":35},"2026-01-14",{"date":675,"type":35},"2019-09-26",{"date":677,"type":20},"2027-11-30",{"name":334,"class":42},{"id":680,"slug":4,"hasResults":11,"nctId":681,"briefTitle":682,"officialTitle":683,"acronym":4,"eligibilityCriteria":684,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":685,"targetDuration":4,"studyType":21,"phases":687,"briefSummary":688,"conditions":689,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":690,"lastUpdatePostDateStruct":691,"startDateStruct":693,"completionDateStruct":695,"leadSponsor":697,"locationsCount":335},"100586083","NCT06910761","Photon Craniospinal Irradiation for the Treatment of Leptomeningeal Disease Secondary to Breast Cancer or Non-small Cell Lung Cancer","Phase II Trial of Photon Craniospinal Irradiation for Leptomeningeal Disease Secondary to Solid Tumor Malignancy","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative\n\n  * Assent, when appropriate, will be obtained per institutional guidelines\n* ≥ 18 years\n* Karnofsky performance status (KPS) ≥ 60\n* Ability to read and understand English or Spanish for questionnaires, or ability to complete questionnaires using certified interpreter\n* Histologically confirmed breast cancer or non-small cell lung cancer\n* Leptomeningeal disease established either radiographically and\u002For CSF cytology\n* Absolute neutrophil count (ANC) ≥ 1,000\u002Fmm\\^3\n* Hemoglobin ≥ 8 g\u002FdL\n* Platelet ≥ 100,000\u002Fmm\\^3\n* Creatinine clearance of ≥ 50 mL\u002Fmin per 24 hour urine test or the Cockcroft-Gault formula\n* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test\n\n  * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 1 month after the last dose of protocol therapy\n\n  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \\> 1 year (women only)\n\nExclusion Criteria:\n\n* Chemotherapy, biological therapy, immunotherapy within 7 days prior to day 1 of protocol therapy\n* Any prior radiation that in the opinion of the investigator unable to respect normal tissue tolerances and preclude craniospinal irradiation\n* Patients with multiple or serious major neurologic symptoms (including encephalopathy) per physician \u002F investigator assessment\n* Patients with extensive, uncontrolled extracranial systemic disease\n* Patients without reasonable systemic treatment options per physician \u002F investigator\n* Other clinically significant uncontrolled illness per opinion of physician \u002F investigator\n* Patients with a history or evidence of HIV infection (unless on effective anti-retroviral therapy with undetectable viral load based on prior tests within 6 months are eligible for this trial)\n* Patients with history or evidence of chronic hepatitis B virus (HBV) infection (unless HBV viral load is undetectable based on prior tests and on suppressive therapy)\n* Patients with a history or evidence of hepatitis C virus (HCV) infection unless treated and cured. (Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load based on prior tests)\n* Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the study are eligible for this trial\n* Females only: Pregnant or breastfeeding\n* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures\n* Unable to undergo MRI brain and spine with gadolinium contrast\n* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility\u002Flogistics)",{"count":686,"type":20},35,[78],"This phase II trial tests how well craniospinal irradiation (CSI) using photon volumetric modulated arc radiotherapy (VMAT) works in treating patients with breast cancer or non-small cell lung cancer (NSCLC) that has spread from the original (primary) tumor to the cerebrospinal fluid and meninges (thin layers of tissue that cover and protect the brain and spinal cord) (leptomeningeal disease). Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. CSI (radiation therapy directed at the brain and spinal cord to kill tumor cells) may be able to target all of the areas of possible leptomeningeal tumor spread. Photon-VMAT-CSI may be an effective treatment option for patients with leptomeningeal disease secondary to breast cancer or NSCLC.",[26,27,28,29,30],"2025-12-02",{"date":692,"type":35},"2025-12-08",{"date":694,"type":35},"2025-05-05",{"date":696,"type":20},"2028-10-02",{"name":419,"class":42},{"id":699,"slug":4,"hasResults":11,"nctId":700,"briefTitle":701,"officialTitle":702,"acronym":4,"eligibilityCriteria":703,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":704,"targetDuration":4,"studyType":21,"phases":705,"briefSummary":706,"conditions":707,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":690,"lastUpdatePostDateStruct":708,"startDateStruct":710,"completionDateStruct":712,"leadSponsor":714,"locationsCount":114},"100422418","NCT04780568","Osimertinib and Tegavivint as First-Line Therapy for the Treatment of Metastatic EGFR-Mutant Non-small Cell Lung Cancer","A Phase Ib Study of AZD9291 (Osimertinib) and BC2059 (Tegavivint) as First-Line Therapy in Patients With Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)","Inclusion Criteria:\n\n* Age \\>= 18 years. Children are excluded from this study because neither dosing nor safety data are currently available for AZD9291 or BC2059 in patients \\\u003C 18 years of age\n* Pathology-confirmed metastatic NSCLC\n* A common activating mutation must be present in the EGFR gene, i.e., exon 19 deletion or L858R. The presence of uncommon EGFR mutations, e.g., G719X, S768I, or L861Q are also permitted if they co-occur with a common activating mutation. Mutation status must be determined using a tumor biopsy by local Clinical Laboratory Improvement Act (CLIA)-certified assessment. Mutations identified by blood-based testing can be provided, but must be verified by tumor biopsy\n* The presence of a concurrent T790M mutation, while uncommon in patients who are naïve to treatment with EGFR TKIs, is also permitted\n* Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2 (Karnofsky \\>= 60%)\n* The patient must be able to swallow pills\n* Life expectancy \\> 3 months\n* Leukocytes \\>= 3,000\u002FmcL\n* Absolute neutrophil count \\>= 1,500\u002FmcL\n* Platelets \\>= 100,000\u002FmcL\n* Hemoglobin \\>= 90 g\u002FL\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit normal (ULN) and up to 3 mg\u002FdL for patients with Gilbert's\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase ALT (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\\u003C 2.5 x institutional ULN and =\\\u003C 5 x institutional ULN for patients with liver metastases\n* Creatinine within 1.5 x ULN OR glomerular filtration rate (GFR) \\>= 50 mL\u002Fmin\u002F1.73 m\\^2 (measured or calculated by Cockcroft and Gault equation) -confirmation of creatinine clearance is only required for patients with creatinine levels above institutional upper limit of normal\n* If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated\n* If history of hepatitis C virus (HCV) infection, it must be treated and have an undetectable viral load\n* Patients with treated brain metastases are asymptomatic and not requiring ongoing treatment\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS)-specific treatment is not required and is unlikely to be required during the first cycle of therapy. Clinical stability on a stable dose of decadron is permitted\n* Patients with a prior or concurrent malignancy whose natural history or treatment will not interfere with the safety or efficacy assessment of the investigational drugs are eligible for this trial\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better\n* Ability to understand and sign a written informed consent document\n\nExclusion Criteria:\n\n* Prior treatment with an EGFR TKI in any setting\n* Patients who have not recovered from adverse events (AEs) due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1), with the exception of alopecia\n* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease\n* Patients who are receiving any other investigational agent or immunotherapy within five half-lives of the compound or 3 months, whichever is greater\n* Patients with an uncontrolled intercurrent illness\n* Patients with psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition as BC2059 or AZD9291. Patients with hypersensitivity to any of the inactive excipients should also be excluded\n* Currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (wash-out periods vary. All patients must try to avoid concomitant use of any medications, herbal supplements and\u002For ingestion of foods with known inducer effects on CYP3A4\n* Pregnant women are excluded from this study because BC2059 has the potential for teratogenic or abortifacient effects. There is also an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with AZD9291 or BC2059. Breastfeeding patients will be excluded\n* Patients with a significant history of cardiovascular disease (e.g., myocardial infarction \\[MI\\], thrombotic or thromboembolic event in the last 6 months)\n* Any of the following cardiac criteria:\n\n  * Mean resting corrected QT interval (corrected QT \\[QTc\\] using Fredericia's formula \\[QTcF\\]) \\> 470 msec. RR is the time from the interval of 1 QRS complex to the next measured in seconds and is commonly calculated as (60\u002FHR)\n  * Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)\n  * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as decompensated heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to prolong the QT interval\n  * Left ventricular ejection fraction (LVEF) \\\u003C lower limit of normal (LLN) as assessed by either multigated acquisition (MUGA) scan or echocardiogram (ECHO)\n* Patients with active malignancies other than NSCLC or patients with prior curatively treated malignancy at high risk of relapse during the study period with the exception of localized squamous or basal cell skin cancers, ductal carcinoma in-situ (DCIS), or indolent cancer currently on observation (i.e. chronic lymphocytic leukemia \\[CLL\\] or low-risk prostate cancer)\n* Any evidence of severe or uncontrolled systemic disease, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection with human immunodeficiency virus (HIV). Screening for chronic conditions is not required\n* Patients who are at risk for impaired absorption of oral medication including, but not limited to, refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9291\n* Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, or requirements\n* Involvement in the planning and\u002For conduct of the study (applies to both investigator staff and\u002For staff at the study site)",{"count":427,"type":20},[77],"This phase Ib trial is to find out the best dose, possible benefits and\u002For side effects of osimertinib and tegavivint as first-line therapy in treating patients with EGFR-mutant non-small cell lung cancer that has spread to other places in the body (metastatic). Osimertinib and tegavivint may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.",[28,30,213,217],{"date":709,"type":35},"2025-12-09",{"date":711,"type":35},"2022-01-18",{"date":713,"type":20},"2029-07-31",{"name":715,"class":42},"Ohio State University Comprehensive Cancer Center",""]