Locally Advanced Non Small Cell Lung Cancer

Brief Summary This prospective, open-label pilot study is designed to evaluate the safety, tolerability, feasibility, and preliminary clinical activity of inhaled cromolyn sodium administered by dry powder inhalation in participants with locally advanced lung cancer. Cromolyn sodium is an FDA-approved mast cell stabilizer with an established safety profile in respiratory disease. Increasing evidence suggests that inflammatory signaling, mast cell activation, and stromal remodeling contribute to tumor progression, immune dysregulation, and resistance to therapy within the lung tumor microenvironment. Modulation of these pathways may represent a novel therapeutic strategy in lung cancer. Approximately 5 to 10 participants with locally advanced lung cancer will receive inhaled cromolyn sodium according to the study protocol. Participants will undergo clinical assessments, safety monitoring, laboratory evaluations, and radiographic imaging in accordance with protocol-defined procedures and standard oncologic care. The primary objective of this pilot study is to evaluate the safety, tolerability, and feasibility of inhaled Cromolyn sodium administration in this patient population. Secondary objectives include exploratory assessment of radiographic response, clinical outcomes, biomarker trends, and potential signals of biological activity. Data generated from this study are intended to support the development of future clinical investigations evaluating the role of mast cell stabilization and tumor microenvironment modulation in lung cancer.

Background: A type of drug called monoclonal antibody immune checkpoint inhibitors are often used in cancer treatment. These drugs help the body s immune system fight cancer by blocking proteins that cause cancer cells to grow. One of these drugs (atezolizumab) is approved to treat certain cancers. Researchers want to find out if lower doses of this drug might provide the same benefit with fewer adverse effects. Objective: To test different doses and timing of atezolizumab for people with cancer. Eligibility: People aged 18 years and older with cancer that has spread locally or to other organs. They must be eligible for treatment with the study drug. Design: Participants will be screened. They will have blood tests and imaging scans. They will provide a sample of tissue from their tumor. Atezolizumab is administered through a tube attached to a needle inserted into a vein in the arm. Participants will take this drug alone or combined with other drugs prescribed for their care. The first 2 treatments will be done per the FDA recommended dose and schedule. Before administering the second dose of the study drug, researchers will check the level of the drug in the participant s blood. Depending on those results, their 3rd dose will be scheduled 2 to 6 weeks later. For the 3rd dose of the study drug, participants will switch to the FDA minimum dosage. Dosages of any other drugs will not change. Researchers will continue to test the levels of the drug in participants blood before each treatment for 16 weeks. After that, these levels will be tested every 3 months. Study treatment may last up to 2 years.

This is a Phase II clinical trial evaluating the efficacy and safety of a new treatment approach for patients with locally advanced non-small cell lung cancer (NSCLC) that has spread to lymph nodes on the opposite side of the chest (known as N3 lymph node involvement). The study will enroll 28 patients aged 18 to 75 years with previously untreated, potentially resectable NSCLC classified as stage IIIB-IIIC. Participants will receive a combination of stereotactic body radiation therapy (SBRT) to the primary lung tumor, followed by two cycles of sintilimab (an immunotherapy drug) plus platinum-based chemotherapy before surgery. The main goals of the study are to see whether this treatment can shrink or eliminate cancer in the contralateral mediastinal lymph node (lymph node downstaging) and allow more patients to undergo curative surgery. Secondary goals include assessing pathological response rates, surgical outcomes, survival, and safety. Patients will be closely monitored during and after treatment, with follow-up visits planned for up to 5 years after surgery.

This is a single-center, prospective, open-label, single-arm phase I exploratory study designed to evaluate the safety and feasibility of a novel central immune-priming radiotherapy strategy in patients with unresectable stage III non-small cell lung cancer (NSCLC). The investigational approach consists of a single 8 Gy/1 fraction radiotherapy dose delivered to the central subregion of the primary tumor, with rapid dose fall-off to keep the peripheral tumor margin dose below 4 Gy, followed by one cycle of PD-(L)1 inhibitor, and then standard concurrent chemoradiotherapy (cCRT) approximately one week later. Patients without disease progression after cCRT will subsequently receive consolidation immune checkpoint inhibitor therapy. The primary objective is to assess the safety and feasibility of this lead-in immune-priming strategy, particularly whether it can be integrated into standard cCRT and subsequent immunotherapy without unacceptable toxicity or treatment delay. The primary endpoint is the dose-limiting toxicity (DLT) rate, with the DLT observation window defined from initiation of the priming radiotherapy to 6-8 weeks after completion of cCRT. Secondary objectives include the on-time initiation rate of cCRT, cCRT completion rate, initiation rate of consolidation immunotherapy, acute and subacute toxicity profile, preliminary efficacy signals, and dynamic changes in peripheral lymphocyte counts. Exploratory analyses will investigate peripheral immune cell subsets, circulating tumor DNA (ctDNA), T-cell receptor (TCR) clonality, cytokine changes, and their associations with toxicity and clinical outcomes. The study will adopt a safety run-in plus expansion design, with an initial cohort of 6 patients and expansion to 24 patients if safety is acceptable.

This is a single institution, single arm phase I/II study of NBTXR3 with radiation therapy for stage I-III advanced non-small cell lung cancer patients who are not candidates for chemotherapy or surgical resection.

This is a Phase II/III randomized clinical trial of Radiosensitivity-Assisted Personalized Adaptive Radiotherapy Technology (RAPART) in locally advanced non-small cell lung cancer patients. The main objective is to test the overall improvement of overall survival (OS), progression free survival (PFS), and local progression free survival (LPFS) of unresectable stage III NSCLC under standard and non-standard mixed treatment conditions compared to conventional 60Gy radiotherapy.

Consolidative immunotherapy following concurrent chemoradiotherapy, based on the PACIFIC trial, has become the standard treatment for locally advanced non-small cell lung cancer (LANSCLC). Radiotherapy strategies for maximizing efficacy and local control require further investigation. This phase III, randomized controlled clinical trial is to investigate the efficacy and safety of hypofractionated chemoradiotherapy followed by consolidative immunotherapy versus conventional fractionated chemoradiotherapy followed by consolidative immunotherapy in LANSCLC patients.

Consolidative immunotherapy following concurrent chemoradiotherapy, based on the PACIFIC trial, has become the standard treatment for locally advanced non-small cell lung cancer (LANSCLC), leading to a 5-year survival rate of over 40%. The optimal timing of radiotherapy combined with immunotherapy still requires further exploration. This phase III, randomized controlled clinical trial is to investigate the efficacy and safety of neoadjuvant immuno-chemotherapy followed by concurrent chemoradiotherapy and consolidative immunotherapy, compared with concurrent chemoradiotherapy and consolidative immunotherapy in LANSCLC patients.

Concurrent chemoradiotherapy (cCRT) is the standard treatment for patients with negative epidermal growth factor receptor (EGFR)-mutated unresectable locally advanced non-small cell lung cancer (LA-NSCLC). However, parts of patients only receive sequential chemoradiotherapy (sCRT) due to various reasons. This phase II study aimed to improve the outcomes of patients receiving sCRT by combining anti-angiogenesis therapy (Anlotinib) during radiotherapy course.We hypothesize that the combination of radiotherapy with anlotinib could improve the 2-year PFS rate from 35% with sCRT to 50. The accrual target was 44 patients.

Surgical intervention remains the primary treatment option for early-stage lung cancer. With the proven efficacy of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC), neoadjuvant immunotherapy has increasingly become a focal point of research. Blocking vascular endothelial growth factor (VEGF) not only inhibits the proliferation of vascular endothelial cells and the formation of new blood vessels but also improves the tumor microenvironment and enhances the infiltration of cytotoxic T lymphocytes within it. Simultaneously targeting the VEGF and PD-L1 pathways can create a synergistic anti-cancer effect. PM8002 injection is a bispecific antibody drug that targets both PD-L1 and VEGF, functioning as a dual-action agent that combines immune suppression and anti-angiogenesis. In patients with locally advanced stage II-III NSCLC, neoadjuvant therapy that concurrently targets PD-L1/VEGF in combination with chemotherapy can improve pathological response rates, provided that the safety of the drug combination is maintained. This approach offers additional benefits to patients, prolongs event-free survival (EFS), and improves prognosis.

This study targeted patients with resectable stage II-IIIA non-small cell lung cancer with EGFR mutation

Our project is going to explore whether management and follow-up of locally advanced/metastatic patients using the patient process management platform can prolong patient survival and improve patient quality of life.

This is a phase II, multicenter, single-arm, non-blind study. To 21 patients with PD-L1 ≥50% locally advanced non-small cell lung cancer, the combination of Pembrolizumab and platinum-doublets will be intravenously administered without radiotherapy to evaluate the efficacy and safety of combination therapy with Pembrolizumab and platinum-doublets.