A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) + Lenvatinib (E7080/MK-7902) + Chemotherapy Compared With Standard of Care as First-line Intervention in Participants With Metastatic Esophageal Carcinoma.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 863
- 试验地点
- 397
- 主要终点
- Part 1 (FP and TP Safety Run-in): Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of pembrolizumab plus lenvatinib plus chemotherapy compared with pembrolizumab plus chemotherapy as first-line intervention in participants with metastatic esophageal carcinoma.
The primary hypotheses are that pembrolizumab plus lenvatinib plus chemotherapy is superior to pembrolizumab plus chemotherapy with respect to overall survival (OS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).
As of Amendment 09, Study MK-7902-014 will begin close out activities. Any participant who discontinues study intervention for any reason will be discontinued from the study without further follow-up. Second Course and treatment beyond disease progression will no longer be offered. No safety concerns contributed to the termination of this study.
详细描述
There will be 2 parts to the study: the cisplatin and 5-fluorouracil (5-FU) (FP) and paclitaxel and cisplatin (TP) Safety Run-in (Part 1) and the Main Study (Part 2). In Part 1 (FP and TP Safety Run-in), participants will be treated with pembrolizumab plus lenvatinib plus FP or TP. Dose-limiting toxicities, safety, and tolerability will be assessed.
In Part 2 (Main Study), participants (not including those participating in Part 1) will be treated with pembrolizumab plus lenvatinib plus chemotherapy or pembrolizumab plus chemotherapy. Efficacy, safety, and tolerability will be assessed.
The protocol-specified analysis of the primary outcome measures was completed with a data cut-off of 08-May-2025 (Primary Completion Date) and served as the final analysis of the primary outcome measures. At the time of the protocol-specified analysis, 368 participants were ongoing in the study and will be included in the End of Trial analysis.
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
- •Has a histologically or cytologically confirmed diagnosis of metastatic squamous cell carcinoma of the esophagus
- •Male participants are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of lenvatinib or 90 days after the last dose of chemotherapy, whichever comes last; 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only and is greater than 90 days post chemotherapy, no male contraception is needed
- •Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP using a contraceptive method that is highly effective or is abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 120 days after the last dose of pembrolizumab, 30 days after the last dose of lenvatinib, or 180 days after the last dose of chemotherapy, whichever occurs last, and agrees not to donate eggs during this period
- •Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP≤150/90 millimeters of mercury (mm Hg) with no change in antihypertensive medications within 1 week prior to randomization
- •Has adequate organ function
排除标准
- •Has had previous therapy for locally advanced unresectable or metastatic esophageal cancer
- •Has locally advanced esophageal carcinoma
- •Has metastatic adenocarcinoma of the esophagus
- •Has direct invasion into adjacent organs such as the aorta or trachea
- •Has radiographic evidence of encasement of a major blood vessel, or of intratumoral cavitation
- •Has perforation risks or significant gastrointestinal (GI) bleeding
- •Has had clinically significant hemoptysis within 3 weeks prior to the first dose of study drug or tumor bleeding within 2 weeks prior to the first dose of study intervention
- •Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention
- •Has GI obstruction, poor oral intake, difficulty in taking oral medication, or existing esophageal stent
- •Has had major surgery, open biopsy, or significant traumatic injury within 3 weeks prior to first dose of study interventions
- •Has received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis
- •Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention; administration of killed vaccines is allowed
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention, or has a history of organ transplant, including allogeneic stem cell transplant
- •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has an active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed
- •Has a history of non-infectious pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
- •Has poorly controlled diarrhea
- •Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
- •Has peripheral neuropathy ≥Grade 2
- •Has a known history of human immunodeficiency virus (HIV) infection
- •Has a known history of Hepatitis B or know active Hepatitis C virus infection
- •Has a weight loss of >20% within the last 3 months
研究组 & 干预措施
Part 2: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 4000 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations or mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] once every 2 weeks [Q2W] for 6 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: Pembrolizumab (Biological)
Part 2: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 4000 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations or mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] once every 2 weeks [Q2W] for 6 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: Oxaliplatin (Drug)
Part 2: Pembrolizumab + Chemotherapy
Participants receive pembrolizumab 400 mg IV every 6 weeks for 18 cycles (each cycle length = 6 weeks, approximately 2 years) plus chemotherapy with FP (cisplatin 80 mg/m^2 IV Q3W for up to 6 administrations [up to ~18 weeks] and 5-FU 4000 mg/m^2 IV Q3W for up to 35 administrations [up to ~2 years]) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2 Q3W for up 6 administrations [up to ~18 weeks]) or in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2 and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] IV Q2W for up to 52 administrations [approximately 2 years]).
干预措施: Leucovorin (Drug)
Part 1: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 400 mg/m^2 followed by 2400 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: Paclitaxel (Drug)
Part 1: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 400 mg/m^2 followed by 2400 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: 5-FU (Drug)
Part 1: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 400 mg/m^2 followed by 2400 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: Pembrolizumab (Biological)
Part 2: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 4000 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations or mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] once every 2 weeks [Q2W] for 6 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: Lenvatinib (Drug)
Part 2: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 4000 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations or mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] once every 2 weeks [Q2W] for 6 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: Cisplatin (Drug)
Part 1: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 400 mg/m^2 followed by 2400 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: Lenvatinib (Drug)
Part 2: Pembrolizumab + Chemotherapy
Participants receive pembrolizumab 400 mg IV every 6 weeks for 18 cycles (each cycle length = 6 weeks, approximately 2 years) plus chemotherapy with FP (cisplatin 80 mg/m^2 IV Q3W for up to 6 administrations [up to ~18 weeks] and 5-FU 4000 mg/m^2 IV Q3W for up to 35 administrations [up to ~2 years]) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2 Q3W for up 6 administrations [up to ~18 weeks]) or in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2 and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] IV Q2W for up to 52 administrations [approximately 2 years]).
干预措施: 5-FU (Drug)
Part 2: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 4000 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations or mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] once every 2 weeks [Q2W] for 6 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: 5-FU (Drug)
Part 2: Pembrolizumab + Chemotherapy
Participants receive pembrolizumab 400 mg IV every 6 weeks for 18 cycles (each cycle length = 6 weeks, approximately 2 years) plus chemotherapy with FP (cisplatin 80 mg/m^2 IV Q3W for up to 6 administrations [up to ~18 weeks] and 5-FU 4000 mg/m^2 IV Q3W for up to 35 administrations [up to ~2 years]) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2 Q3W for up 6 administrations [up to ~18 weeks]) or in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2 and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] IV Q2W for up to 52 administrations [approximately 2 years]).
干预措施: Oxaliplatin (Drug)
Part 1: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 400 mg/m^2 followed by 2400 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: Cisplatin (Drug)
Part 2: Pembrolizumab + Chemotherapy
Participants receive pembrolizumab 400 mg IV every 6 weeks for 18 cycles (each cycle length = 6 weeks, approximately 2 years) plus chemotherapy with FP (cisplatin 80 mg/m^2 IV Q3W for up to 6 administrations [up to ~18 weeks] and 5-FU 4000 mg/m^2 IV Q3W for up to 35 administrations [up to ~2 years]) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2 Q3W for up 6 administrations [up to ~18 weeks]) or in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2 and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] IV Q2W for up to 52 administrations [approximately 2 years]).
干预措施: Paclitaxel (Drug)
Part 2: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 4000 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations or mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] once every 2 weeks [Q2W] for 6 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: Leucovorin (Drug)
Part 2: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 4000 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations or mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] once every 2 weeks [Q2W] for 6 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: Levoleucovorin (Drug)
Part 2: Pembrolizumab + Lenvatinib + Chemotherapy
In the Induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 4000 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) IV every 3 weeks for 4 administrations or mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] once every 2 weeks [Q2W] for 6 administrations at the investigator's discretion (approximately 12 weeks). In the Consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
干预措施: Paclitaxel (Drug)
Part 2: Pembrolizumab + Chemotherapy
Participants receive pembrolizumab 400 mg IV every 6 weeks for 18 cycles (each cycle length = 6 weeks, approximately 2 years) plus chemotherapy with FP (cisplatin 80 mg/m^2 IV Q3W for up to 6 administrations [up to ~18 weeks] and 5-FU 4000 mg/m^2 IV Q3W for up to 35 administrations [up to ~2 years]) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2 Q3W for up 6 administrations [up to ~18 weeks]) or in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2 and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] IV Q2W for up to 52 administrations [approximately 2 years]).
干预措施: Pembrolizumab (Biological)
Part 2: Pembrolizumab + Chemotherapy
Participants receive pembrolizumab 400 mg IV every 6 weeks for 18 cycles (each cycle length = 6 weeks, approximately 2 years) plus chemotherapy with FP (cisplatin 80 mg/m^2 IV Q3W for up to 6 administrations [up to ~18 weeks] and 5-FU 4000 mg/m^2 IV Q3W for up to 35 administrations [up to ~2 years]) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2 Q3W for up 6 administrations [up to ~18 weeks]) or in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2 and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] IV Q2W for up to 52 administrations [approximately 2 years]).
干预措施: Levoleucovorin (Drug)
结局指标
主要结局
Part 1 (FP and TP Safety Run-in): Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Up to ~21 days
Hematologic DLTs are defined as Grade 4 neutropenia lasting for ≥7 days, Grade 3 or Grade 4 febrile neutropenia, Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia, or Grade 4 anemia. Other nonhematologic toxicities considered a DLT include any other Grade 4 or Grade 5 toxicity, Grade 3 toxicities lasting \>3 days (excluding nausea, vomiting, and diarrhea controlled by medical intervention within 72 hours, and Grade 3 rash in the absence of desquamation with no mucosal involvement), Grade 3 hypertension not able to be controlled by medication, ≥Grade 3 gastrointestinal perforation, ≥Grade 3 wound dehiscence requiring medical or surgical intervention, any grade thromboembolic event or any Grade 3 nonhematologic laboratory value requiring medical intervention or hospitalization. The number of participants in Part 1 with DLTs will be presented.
Part 2 (Main Study): Overall Survival (OS) in all Participants
时间窗: Up to ~48 months
OS is defined as the time from randomization to death due to any cause. OS in Part 2 for all randomized participants will be presented.
Part 1 (FP and TP Safety Run-in): Number of Participants With Adverse Events (AEs)
时间窗: Up to ~53 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 1 with AEs will be presented.
Part 1 (FP and TP Safety Run-in): Number of Participants who Discontinued Study Treatment Due to an AE
时间窗: Up to ~53 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 1 who discontinue study treatment due to an AE will be presented.
Part 1 (FP and TP Safety Run-in): Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Up to 21 days
A DLT is defined as a specific adverse event graded for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Hematologic DLTs are defined as Grade 4 neutropenia lasting for ≥7 days, Grade 3 or Grade 4 febrile neutropenia, Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia, or Grade 4 anemia. Other nonhematologic toxicities considered a DLT include any other Grade 4 or Grade 5 toxicity, Grade 3 toxicities lasting \>3 days (excluding nausea, vomiting, and diarrhea controlled by medical intervention within 72 hours, and Grade 3 rash in the absence of desquamation with no mucosal involvement), Grade 3 hypertension not able to be controlled by medication, ≥Grade 3 gastrointestinal perforation, ≥Grade 3 wound dehiscence requiring medical or surgical intervention, any grade thromboembolic event or any Grade 3 nonhematologic laboratory value requiring medical intervention or hospitalization. The number of participants in Part 1 with DLTs are presented.
Part 1 (FP and TP Safety Run-in): Number of Participants With Adverse Events (AEs)
时间窗: Up to 43 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 1 with AEs will be presented.
Part 1 (FP and TP Safety Run-in): Number of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to 22 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants in Part 1 who discontinue study treatment due to an AE will be presented.
Part 2 (Main Study): Overall Survival (OS) in All Participants
时间窗: Up to 42 months
OS is defined as the time from randomization to death due to any cause. OS in Part 2 for all randomized participants are presented based on the Kaplan-Meier method for censored data.
次要结局
- Part 2 (Main Study): Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in All Participants(Up to 42 months)
- Part 2 (Main Study): Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in All Participants(Up to 42 months)
- Part 2 (Main Study): Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in All Participants(Up to 42 months)
- Part 2 (Main Study): OS in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10(Up to 42 months)
- Part 2 (Main Study): PFS Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10(Up to 42 months)
- Part 2 (Main Study): ORR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10(Up to 42 months)
- Part 2 (Main Study): DOR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10(Up to 42 months)
- Part 2 (Main Study): Number of Participants With AEs(Up to 43 months)
- Part 2 (Main Study): Number of Participants Who Discontinued Study Treatment Due to an AE(Up to 22 months)
- Part 2 (Main Study): Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in all Participants(Up to ~42 months)
- Part 2 (Main Study): Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR in all Participants(Up to ~42 months)
- Part 2 (Main Study): Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR in all Participants(Up to ~42 months)
- Part 2 (Main Study): OS in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10(Up to ~48 months)
- Part 2 (Main Study): PFS per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10(Up to ~42 months)
- Part 2 (Main Study): ORR per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10(Up to ~42 months)
- Part 2 (Main Study): DOR per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10(Up to ~42 months)
- Part 2 (Main Study): Number of Participants With AEs(Up to ~53 months)
- Part 2 (Main Study): Number of Participants who Discontinued Study Treatment Due to an AE(Up to ~53 months)