Kolambugan

Researchers are evaluating the safety and effectiveness of combining durvalumab and domvanalimab compared to durvalumab plus placebo in adults with locally advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) whose disease has not worsened after definitive platinum-based concurrent chemoradiation therapy. This Phase III, randomized, double-blind, placebo-controlled, international study involves multiple centers. Participants receive intravenous infusions of durvalumab and domvanalimab or durvalumab and placebo. The treatments are given after patients have completed concurrent platinum-based chemotherapy and radiation therapy with a total radiation dose of approximately 60 Gy. The study monitors patients over time to assess treatment effects and safety. During the study, participants undergo evaluations including tumor tissue analysis for PD-L1 status, performance status assessments, and monitoring of organ and marrow function. The main outcome measured is progression-free survival up to 8 years after randomization. Researchers also monitor for any adverse effects and disease progression throughout the study period.

Researchers are evaluating the effectiveness and safety of Datopotamab Deruxtecan (Dato-DXd) with or without durvalumab compared to the investigator's choice chemotherapy combined with pembrolizumab in patients who have PD-L1 positive locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC). This Phase III, randomized, open-label, international study aims to see if adding durvalumab to Dato-DXd can help patients live longer without their cancer worsening or simply live longer compared to standard chemotherapy with pembrolizumab. The study also examines how the treatments and cancer impact patients' quality of life. Participants will be randomly assigned to one of three treatment groups: Dato-DXd plus durvalumab, Dato-DXd alone, or investigator's choice chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) combined with pembrolizumab. All treatments are given by intravenous infusion. The study design includes stratification based on geographic location, disease-free interval history, and prior PD-1/PD-L1 treatment for early-stage TNBC. During the study, participants will have regular assessments to monitor their disease status using RECIST 1.1 criteria and undergo imaging reviewed by blinded independent central review. Researchers will track progression-free survival, quality of life, safety, and other health measures over an anticipated period of up to 33 months. Participants must provide tumor samples for PD-L1 testing, and safety monitoring will continue throughout the study.

Researchers are evaluating the effectiveness of camizestrant compared to standard endocrine therapy in patients with early breast cancer that is estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-). These patients have an intermediate or high risk of cancer recurrence and have already completed local treatments such as surgery and possibly chemotherapy, alongside at least 2 years and up to 5 years of standard adjuvant endocrine therapy. The study is a Phase III, open-label trial designed to assess outcomes over a long term. Participants will be randomly assigned to receive either camizestrant, an oral selective estrogen receptor degrader, or one of several standard endocrine therapies including tamoxifen, anastrozole, letrozole, or exemestane, administered according to local approved guidelines. The treatment duration for both groups is planned to last 60 months. Eligible patients may have previously used CDK4/6 inhibitors, and the study will specifically include those with intermediate or high risk of recurrence as determined by clinical and biological markers. During the study, participants will be monitored for up to 10 years from the last patient's randomization to evaluate invasive breast cancer-free survival. Additional outcomes include invasive disease-free survival, distant relapse-free survival, overall survival, safety, and clinical outcome assessments. The study involves ongoing assessments of health status, treatment effects, and safety to determine the long-term benefits and risks of camizestrant compared to standard therapies.

Researchers are investigating the safety and effectiveness of Dato-DXd combined with osimertinib or alone compared to platinum-based doublet chemotherapy in treating adults with epidermal growth factor receptor-mutated (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC). This Phase III, open-label study includes participants whose disease has worsened despite prior osimertinib treatment. The goal is to evaluate progression-free survival (PFS) over up to 2.5 years. Participants are randomly assigned to one of three groups: Dato-DXd plus osimertinib, Dato-DXd alone, or platinum-based doublet chemotherapy. Dato-DXd and chemotherapy drugs (pemetrexed, carboplatin, or cisplatin) are given by intravenous infusion, while osimertinib is taken orally. Treatment continues until the cancer progresses based on imaging, unacceptable side effects occur, or other reasons require stopping treatment. After stopping the study drugs, participants will have an end-of-treatment visit within 35 days and safety follow-up about one month later. During the trial, researchers will monitor participants with radiological scans and assess progression-free survival. Safety evaluations will continue after treatment ends to detect any side effects. The study includes adults aged 18 to 130 years with good performance status and adequate organ function who have progressed on prior osimertinib therapy. The total study duration includes treatment and follow-up periods to ensure thorough assessment of treatment effects and safety.

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm of the study is 7 years. Eligible patients must have intermediate-high or high risk of recurrence as defined by specified clinical and biologic criteria. Concurrent use of abemaciclib is permitted in both arms. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.

Researchers are evaluating the safety and tolerability of trastuzumab deruxtecan (T-DXd) combined with immunotherapy agents, with or without chemotherapy, in patients with HER2 over-expressing non-small cell lung cancer (NSCLC). This Phase Ib study also looks at how effective these combinations may be. The study focuses on patients with advanced or metastatic non-squamous NSCLC who have measurable disease and no known actionable genomic alterations with approved therapies. Patients must have an ECOG performance status of 0 or 1 and be treatment-nave for advanced disease. The study is divided into multiple parts. Part 1 involves dose escalation to assess safety and recommended doses of T-DXd combined with durvalumab and chemotherapy agents (cisplatin, carboplatin, or pemetrexed), but no further patients will be enrolled in this part. Parts 3, 4, and 5 evaluate T-DXd with different immunotherapy agents (volrustomig or rilvegostomig), with or without carboplatin, and explore dose optimization and priming versus flat dosing regimens. Some parts include dose escalation, dose expansion, and optional arms at the sponsor's discretion. Participants will receive study drugs via intravenous infusion and undergo evaluations for safety, tolerability, and response. Researchers will monitor adverse events and serious adverse events for about 20 months from consent to determine the recommended phase 2 dose. Patients will be assessed for measurable disease using RECIST 1.1 criteria, and organ and bone marrow function will be checked. Safety monitoring includes cardiac assessments and screening for infections. The study aims to gather data on tolerability and potential efficacy over the treatment period.