Locally Advanced

The Phase 2 monotherapy portion of this study is currently enrolling and will evaluate the efficacy and safety of PC14586 (INN rezatapopt) in participants with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation. The Phase 1 portion of the study will assess the safety, tolerability and preliminary efficacy of multiple dose levels of rezatapopt as monotherapy and in Phase 1b in combination with pembrolizumab.

Purpose: To evaluate the efficacy and safety of neoadjuvant treatment with iparomlimab and tuvonralimab (QL1706), a dual PD1and CTLA4 bispecific antibody, in combination with paclitaxel and either cisplatin or carboplatin (TP/TC regimen) for patients with locally advanced cervical cancer. Eligibility Criteria: Women aged 18 to 70 years with newly diagnosed, histologically confirmed cervical cancer (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma), FIGO stage IB3 or IIA2, with no evidence of significant lymph node involvement (pelvic and paraaortic lymph nodes \<1.5 cm in short diameter), and who have not received any prior anticancer therapy. Study Procedures: Participants will receive up to 4 cycles of QL1706 plus TP/TC chemotherapy (once every 3 weeks) prior to surgery. After 2 cycles, clinical assessment will be performed to evaluate tumor response. If tumor shrinkage is observed, treatment may continue for 2 additional cycles, followed by imaging evaluation. Depending on the response, participants with complete or partial response may undergo less extensive surgery (cervical conization plus sentinel lymph node biopsy) rather than standard radical hysterectomy. After surgery, participants who achieve a major pathological response will receive QL1706 maintenance therapy as a single agent for up to 8 additional cycles (once every 3 weeks). For participants with insufficient tumor response, standard radical hysterectomy will be performed. Postoperative adjuvant therapy (radiation or chemotherapy) will follow standard clinical guidelines. Primary and Secondary Objectives: The primary endpoint is the pathological complete response (pCR) rate in the resected tissue following neoadjuvant treatment. Secondary endpoints include safety (treatment related adverse events), objective response rate (ORR), 3 years overall survival, 3 years disease free survival, and quality of life. Study Duration: Total participation time depends on treatment response and surgical scheduling, with an expected duration of approximately 9 to 12 months (including neoadjuvant treatment, surgery, and potential maintenance therapy).

The aim of the study is to evaluate the impact of digital monitoring of self-reported symptoms (PROs) on the adjustment of treatment management in patients treated with cabozantinib plus nivolumab for advanced clear cell renal cell carcinoma (RCC) in real life during the first 3 months of combined treatment

This study, the first clinical trial of AVZO-103, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and antitumor activity of AVZO-103 when administered intravenously as a monotherapy and in combination therapy to patients with locally advanced or metastatic urothelial cancer or other solid tumors.

This study, the first clinical trial of AVZO-1418, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and antitumor activity of AVZO-1418 when administered intravenously as a monotherapy and potentially in combination therapy to patients with locally advanced or metastatic epithelial solid tumors.

This is a phase 2, pilot, randomized, open-label 3-arm study to assess the safety, tolerability, and efficacy of CUE-101 monotherapy, and CUE-101 in combination with pembrolizumab as neoadjuvant therapy in HLA-A\*0201-positive treatment naive participants with locally advanced HPV-16 associated head and neck squamous cell carcinoma (HNSCC).

This is a multi-center, open-label study to investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary activity of REC-1245 administered orally on a once daily (QD) schedule in participants with unresectable, locally advanced, or metastatic solid tumors.

The purpose of this research study is to determine if lattice radiation therapy (LRT) will provide better treatment for bulky (large) tumors than current standard of care radiotherapy.

Determine anti-tumor efficacy by characterizing response rates on positron emission tomography (PET) following three cycles of induction immunotherapy with cemiplimab and fianlimab without chemotherapy for locally advanced non-small cell lung cancer (LA-NSCLC).

The goal of this clinical investigation is to learn if a new type of radiotherapy works to treat pancreatic cancer that cannot be removed surgically. It will also learn about the safety of the new treatment when combined with chemotherapy. The treatment involves injecting a radioactive implant (medical device) directly into the pancreatic tumour on one occasion only. The main questions it aims to answer are: * Is the new treatment safe and tolerable when used in combination with standard of care chemotherapy. * Is it feasible to inject the new treatment directly into a patient's pancreatic tumour. * What is the impact of this new treatment on a patient's quality of life including a pain evaluation. * To assess how the pancreatic tumour responds to the treatment during the 3 month follow up. Participants will: * Participate in the research study for approximately 7 months and will receive standard of care chemotherapy throughout their participation. * Participants will initially receive standard of care chemotherapy which will be stopped after 2 months to reassess the tumor by a multidisciplinary tumor board. Chemotherapy will resume and the test device will be administered between chemotherapy treatments. The new treatment involves a single injection of the radioactive implant directly into the pancreatic tumour. Following treatment, the participant's standard of care chemotherapy will resume. * Participants will attend follow up visits over 3 months. * Participants will visit the clinic on 8 separate occasions and on one occasions, will remain in hospital for 2 nights/3 days to receive treatment with the new radiotherapy device and to monitor for safety. * Participants will complete questionnaires to check how the treatment is affecting their daily lives and pain levels. * Participants will undergo different types of imaging (scans) such as CT, MRI. * Participants will have bloods and urine taken to monitor safety.

The purpose of this clinical trial is to determine whether using chemotherapy followed by stereotactic ablative body radiation therapy (SABR) and tumor treating fields (TTF) will slow tumor growth in people with locally advanced pancreas cancer. All participants will receive SABR therapy once per day for five days and use the TTF system for at least 18 hours per day starting on the first day of SABR until the tumor progresses or severe toxicity develops.

Multinational, randomized, controlled, open-label, multicenter phase II trial. Eligible patients will be randomized in a ratio of 1:1 to Experimental Arm (FDG-PET-based small volume accelerated radiotherapy with concurrent standard of care chemotherapy) or Conventional Arm (standard FDG-PET-based radiotherapy with concurrent standard of care chemotherapy). Patients showing complete response, partial response, or stable disease following chemoradiotherapy will receive standard of care consolidation therapy with durvalumab (fixed dose of 1500 mg q4w) for up to 12 months or until progression of disease, unacceptable toxicity, patient´s wish, or investigator´s decision, whichever comes first. After end of durvalumab therapy, patients will undergo safety follow up for 90 (+7) days followed by survival follow up until overall end of study. Overall end of study will be reached 24 months after the last patient has started durvalumab therapy. Patients showing PD following chemoradiotherapy will be treated according to investigator´s decision but will be followed up until overall end of study.

This is an observational study to validate target axillary dissection (TAD) in locally advanced tumors (cN2 and/or cT4).

The goal of this phase 2 study is to learn about the efficacy and safety of short-course radiotherapy (SCRT) sequential Penpulimab in combination with CAPEOX in the neoadjuvant treatment of microsatellite stable (MSS) locally advanced rectal cancer. The main question it aims to answer is the role of immune checkpoint inhibitors in the neoadjuvant treatment of MSS rectal cancer. Participants will receive neoadjuvant treatment of SCRT sequential Penpulimab in combination with CAPEOX. Participants will undergo a clinical re-staging assessment at the end of neoadjuvant therapy to determine whether to adopt a watch-and-wait strategy or undergo radical surgery.

This study is a prospective, observational, real-world, multi-center study planning to enroll 90 patients. The study will observe and document patients' actual clinical practices in receiving Iparomlimab and Tuvonralimab Injection (QL1706). The primary objectives are to evaluate the safety and effectiveness of Iparomlimab and Tuvonralimab Injection (QL1706) in treating locally advanced or metastatic solid tumors.

This study aims to evaluate the effectiveness and safety of a preoperative treatment (called neoadjuvant therapy) combining four drugs-nab-paclitaxel, oxaliplatin, S-1, and sintilimab-for patients with locally advanced, resectable early-onset gastric cancer (diagnosed at age 45 or younger). All participants will receive this drug combination before undergoing surgery to remove the tumor. The goal is to shrink the tumor, increase the chance of complete surgical removal, and improve long-term outcomes. This is a single-arm, open-label, phase II clinical trial, meaning all participants will receive the same treatment, and both doctors and patients will know what drugs are being used. The study is being conducted at Peking University People's Hospital.

For unresectable locally-advanced non-small cell lung cancer, chemoradiotherpay plus immunotherapy is recommended by PACIFIC trial. However, it is unclear whether surgery can provide survival benefit for patients with tumors initially unresectable transformed into resectable ones after chemoimmunotherapy. This trial aims to investigate the efficacy and safety of the therapeutic regimen of chemoimmunotherapy plus surgery.

Radical radiotherapy is critical for locally advanced non small cell lung cancer(NSCLC ). Our previous sturdy indicated that patients who received induction immunotherapy and subsequent radiotherapy suffered higher proportion of pneumonitis.Grade 2 or more pneumonitis patients have worse prognosis. It is urged to optimize the radiotherapy dose and target volume for patients treated with immunotherapy and radiotherapy. According to retrospective and prospective studies, omitting CTV radiation is feasible for patients undergoing concurrent radio-chemotherapy for locally advanced NSCLC. It is postulated that omitting CTV radiation for patients responded to induction therapy with immunotherapy and chemotherapy will have less pneumonitis without sacrificing the local control rate. Omitting CTV may also retain better immune function which will facilitate the immunotherapy.

In this study, we propose to conduct an ambispective study to analyze the safety of preserved renal unit surgery combined with postoperative adjuvant radiotherapy in patients with limited stage ureteral cancer with high risk factors, and the efficacy analysis compared with traditional radical surgery. It is hoped that a treatment method that preserves patients' renal function to improve the tolerance of subsequent drug therapy without decreasing the effect of tumor treatment can be achieved in patients with high-risk factors.

This is a single arm, open-label, prospective clinical trial to evaluate the combination of neoadjuvant short-course radiotherapy and toripalimab (PD-1 antibody) for locally advanced rectal cancer (LARC) patients with high risk factors. A total of 53patients will be enrolled in this trial to receive 5\*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody. Then they will receive the TME surgery and another 2 cycles of CAPOX chemotherapy. The primary end point is the rate of pathological complete response (pCR). The long-term prognosis and adverse effects will also be evaluated and analyzed.

The goal of this clinical trial is to explore the value of molecular residual disease (MRD) monitoring based on ctDNA in borderline resectable or locally advanced pancreatic cancer. The main questions it aims to answer are: * prognostic value of baseline MRD; * the role of MRD dynamic changes after treatment in guiding treatment. Peripheral blood derived from participants will be obtained for MRD test before conversion therapy initiation and at the first imaging assessment after chemotherapy.