A Phase 2, Randomized, Open-label, Platform Study Utilizing a Master Protocol to Evaluate Novel Immunotherapy Combinations in Participants With Previously Untreated, Locally Advanced/Metastatic, Programmed Death Ligand 1-Selected Non-Small-Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 351
- 试验地点
- 99
- 主要终点
- Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This study will monitor the safety of novel immunotherapy combinations in participants with Programmed death ligand-1 (PD L-1) high (Tumor cells [TC]/ Tumor proportion score [TPS] >= 50%), previously untreated, unresectable, locally advanced or metastatic non-small cell lung cancer (NSCLC). Drug name mentioned as Belrestotug, GSK4428859A, and EOS884448 are all interchangeable for the same compound. In the rest of the document, the drug will be referred to as Belrestotug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed diagnosis of locally advanced unresectable NSCLC not eligible for curative surgery and/or definitive radiotherapy with or without chemotherapy or metastatic NSCLC (squamous or non squamous)
- •No prior systemic therapy for their locally advanced or metastatic NSCLC
- •Provides a fresh tumor tissue sample or archival sample collected within 2 years prior to screening
- •PD-L1-high (TC/TPS >= 50%) tumor
- •Measurable disease based on RECIST 1.1, as determined by the investigator
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- •Adequate Baseline organ function
- •Female participants of childbearing potential must use adequate contraception
排除标准
- •Has NSCLC with a tumor that harbors any of the following molecular alterations: EGFR and /or ALK translocations mutations that are sensitive to available targeted inhibitor therapy, Any other known genomic aberrations or oncogenic driver mutations for which a locally approved targeted therapy is available for first-line treatment of locally advanced or metastatic NSCLC.
- •Had major surgery within 4 weeks or lung radiation of >30 Gy therapy within 6 months prior to the first dose of study intervention
- •Received prior therapy with any immune checkpoint inhibitors
- •Never smoked, defined as smoking <100 tobacco cigarettes in a lifetime
- •Has an invasive malignancy or history of invasive malignancy other than the disease under study within the last 5 years (clinical exceptions apply as per protocol)
- •Symptomatic, untreated, or actively progressing, brain metastases or any leptomeningeal disease (regardless of symptomatology, treatment status, or stability)
- •Autoimmune disease or syndrome that required systemic treatment within the past 2 years
- •Receiving systemic steroid therapy <= 3 days prior to first dose of study intervention or any form of immunosuppressive medication
- •Received any live vaccine <= 30 days prior to first dose of study intervention
- •Any history of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
- •History or evidence of cardiac abnormalities
- •Current unstable liver or biliary disease
- •Severe infection within 4 weeks prior to the first dose of study intervention
- •Positive for tuberculosis, human immunodeficiency virus (HIV) infection, hepatitis B surface antigen, or hepatitis C
- •Has advanced, symptomatic, or visceral spread and is considered to be at imminent risk of life-threatening complications (including, but not limited to, massive uncontrolled effusions [e.g., pleural, pericardial, peritoneal])
- •Is currently participating in or has participated in a study of an investigational therapy within 4 weeks prior to the first dose of study intervention
- •Has a history of allogeneic tissue/stem cell transplant or solid organ transplant
研究组 & 干预措施
Pembrolizumab Monotherapy
Participants will be administered with pembrolizumab as monotherapy in a fixed dose.
干预措施: Pembrolizumab (Drug)
Dostarlimab Monotherapy
Participants will be administered with dostarlimab as monotherapy in a fixed dose.
干预措施: Dostarlimab (Drug)
Substudy 1A
Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose A).
干预措施: Dostarlimab (Drug)
Substudy 1A
Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose A).
干预措施: Belrestotug (Drug)
Substudy 1B
Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose B).
干预措施: Dostarlimab (Drug)
Substudy 1B
Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose B).
干预措施: Belrestotug (Drug)
Substudy 1C
Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose C).
干预措施: Dostarlimab (Drug)
Substudy 1C
Participants will be administered with dostarlimab in a fixed dose followed by belrestotug in a fixed dose (Dose C).
干预措施: Belrestotug (Drug)
Substudy 2A
Participants will be administered with dostarlimab, fixed dose belrestotug, and fixed dose nelistotug
干预措施: Dostarlimab (Drug)
Substudy 2A
Participants will be administered with dostarlimab, fixed dose belrestotug, and fixed dose nelistotug
干预措施: Belrestotug (Drug)
Substudy 2A
Participants will be administered with dostarlimab, fixed dose belrestotug, and fixed dose nelistotug
干预措施: Nelistotug (Drug)
结局指标
主要结局
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Up to 228 weeks
Number of Participants with TEAEs or SAEs leading to dose modifications or treatment discontinuation
时间窗: Up to 228 weeks
次要结局
未报告次要终点