A Phase II/III, Multicenter, Randomized, Placebo-controlled Study of Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) as First-line Treatment of Biliary Tract Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 309
- 试验地点
- 99
- 主要终点
- Safety Run-in Part: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
研究概览
简要总结
Study consisted of an open-label, safety run-in part and a randomized, double-blind, placebo-controlled Phase 2/3 part. In the Phase 2/3 part, the study was evaluated whether bintrafusp alfa in combination with the current standard of care (SoC) (gemcitabine plus cisplatin) improves overall survival (OS) in chemotherapy and immunotherapy-naïve participants with locally advanced or metastatic Biliary Tract Cancer (BTC) compared to placebo, gemcitabine and cisplatin.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Are participants with histologically or cytologically confirmed locally advanced or metastatic BTC
- •Participants must have available tumor tissue (primary or metastatic) (archival or fresh biopsies) before the first administration of study treatment
- •At least 1 measurable lesion according to RECIST 1.1
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at study entry and at Week 1, Day 1 prior to dosing
- •Life expectancy of >= 12 weeks, as judged by the Investigator
- •Adequate hematological function, hepatic function, renal function, coagulation function as defined in the protocol
- •Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be treated and on a stable dose of antivirals
- •Other protocol defined inclusion criteria could apply
排除标准
- •Previous and/or intercurrent cancers
- •Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression
- •Participants with symptomatic central nervous system (CNS) metastases
- •Significant acute or chronic infection including known history of positive test for human immunodeficiency virus (HIV), active tuberculosis, uncontrolled biliary infection and active bacterial or fungal infection requiring systemic therapy (with the exception of hepatitis B and hepatitis C) requiring systemic therapy at study entry and at Week 1 Day 1 prior to dosing.
- •Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
- •History of or concurrent interstitial lung disease
- •History of hypersensitivity reactions to bintrafusp alfa, anaphylaxis, or recent (within 5 months) uncontrolled asthma, cardiovascular/cerebrovascular disease
- •Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before randomization
- •Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints)
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Safety Run-In Part: M7824 + Gemcitabine + Cisplatin
干预措施: M7824 (Drug)
Safety Run-In Part: M7824 + Gemcitabine + Cisplatin
干预措施: Gemcitabine (Drug)
Safety Run-In Part: M7824 + Gemcitabine + Cisplatin
干预措施: Cisplatin (Drug)
Double-blinded Part: M7824 + Gemcitabine + Cisplatin
干预措施: M7824 (Drug)
Double-blinded Part: M7824 + Gemcitabine + Cisplatin
干预措施: Gemcitabine (Drug)
Double-blinded Part: M7824 + Gemcitabine + Cisplatin
干预措施: Cisplatin (Drug)
Double-blinded Part: Placebo + Gemcitabine + Cisplatin
干预措施: Placebo (Drug)
Double-blinded Part: Placebo + Gemcitabine + Cisplatin
干预措施: Gemcitabine (Drug)
Double-blinded Part: Placebo + Gemcitabine + Cisplatin
干预措施: Cisplatin (Drug)
结局指标
主要结局
Safety Run-in Part: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
时间窗: Day 1 up to Day 21 of Cycle 1 (each Cycle is of 21 days)
A DLT is a toxicity related to the study intervention that meets the following criteria as evaluated in the open-label, safety run-in: Grade 3 or 4 Immune-related adverse event (irAE) that needs permanent discontinuation of M7824 treatment; a malignant skin lesion induced by M7824 that is local and can be resected with a negative resection margin is not a DLT; Grade 3 or 4 nonhematologic toxicity other than irAE, A life threatening hematological toxicity (unless clearly attributable to chemotherapy alone), which is hardly medically manageable, including a bleeding event resulting in urgent intervention and admission to an intensive care unit and Grade 5 toxicity.
Double-blind Part: Overall Survival
时间窗: Time from study day 1 up to data cutoff (assessed up to 609 days)
Overall Survival was defined as the time from study day 1 to the date of death due to any cause. The overall survival was analyzed by using the Kaplan-Meier method.
次要结局
- Double-blind Part: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)(Time from randomization of study drug until the first documentation of PD or death, assessed up to 609 days)
- Safety Run-in Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (SAEs) and Treatment Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0(Time from first treatment up to data cutoff (assessed up to 609 days))
- Double-blind Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (SAEs), Treatment Related TEAEs and Adverse Events of Special Interest (AESIs) According to NCI-CTCAE Version 5.0(Time from first treatment up to data cutoff (assessed up to 609 days))
- Safety Run-in Part: Number of Participants With Grade Greater Than or Equal (>=) 3 Laboratory Abnormalities(Time from first treatment up to data cutoff (assessed up to 609 days))
- Double-blind Part: Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)(Time from randomization of study drug up to data cut off (assessed up to 609 days))
- Double-blind Part: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)(From first documented objective response to PD or death due to any cause, assessed up to 609 days)
- Double-blind Part: Durable Response of at Least 6 Months According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator(Time from first treatment assessed up to 1148 days)