A Phase 1b Multi-cohort Study of the Combination of Pembrolizumab (MK-3475) Plus Binimetinib Alone or the Combination of Pembrolizumab Plus Chemotherapy With or Without Binimetinib in Participants With Metastatic Colorectal Cancer (KEYNOTE-651)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 116
- 试验地点
- 14
- 主要终点
- Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study is to determine safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) for the following combinations: pembrolizumab plus binimetinib (Cohort A), pembrolizumab plus mFOLFOX7 (oxaliplatin 85 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2) (Cohort B), pembrolizumab plus mFOLFOX7 and binimetinib (Cohort C), pembrolizumab plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate]400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) (Cohort D), and pembrolizumab plus FOLFIRI and binimetinib (Cohort E).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •At least 18 years of age
- •Has a histologically-confirmed, unresectable or metastatic (Stage IV American Joint Committee on Cancer [AJCC seventh edition]) colorectal cancer (CRC)
- •Has a locally determined non microsatellite instability high/ proficient mismatch repair (non-MSI-H/pMMR) tumor status
- •Has at least 1 radiologically measurable lesion as defined by RECIST 1.1
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Has a life expectancy of at least 3 months
- •Has the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption.
- •Has adequate organ function
- •Male participants must agree to use contraception during the treatment period and for ≥180 days, after the last dose of study treatment and refrain from donating sperm during this period. Male participants with pregnant partners must agree to use a condom
- •Female participants eligible to participate if not pregnant, not breastfeeding, and is not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees to follow contraceptive guidance during the treatment period and for ≥180 days after the last dose of study treatment
- •Participants for Cohort A:
- •Has been previously treated with fluoropyrimidine, irinotecan, and oxaliplatin
- •Participants for Cohorts B and C:
- •Must not have received prior systemic chemotherapy for Stage IV CRC
- •Participants for Cohorts D and E:
- •Must have been previously treated with 1 line of therapy including a fluoropyrimidine plus an oxaliplatin-based regimen
- •Participants for Cohorts A, C, and E:
- •Have a 12-lead electrocardiogram (ECG) and echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed by the investigator or other qualified person to evaluate cardiac function prior to enrollment in the study
排除标准
- •Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of MK-3475
- •Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (prior to the first dose of study therapy, or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Gr 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
- •Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
- •Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has a known hypersensitivity, intolerability or contraindication to any component of study treatment, including premedication
- •Has any active infection requiring systemic therapy
- •Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- •Has received prior therapy with compounds targeting programmed death (PD)-1, PD-L1, PD-L2, or a mitogen-activated protein kinase (MAPK) pathway inhibitor
- •Has an autoimmune disease that has required systemic treatment in the past 2 years with use of disease modifying agents, corticosteroids, or immunosuppressive drugs
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization
- •Has known history of human immunodeficiency virus (HIV) infection
- •Has a known history of Hepatitis B
- •Has received live vaccine within 30 days of the planned start of study therapy
- •Has undergone major surgery and has not recovered adequately from any toxicity and/or complications from the intervention prior to starting study therapy
- •Has baseline peripheral neuropathy/paresthesia
- •Has any medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol, or complete the study.
- •Has symptomatic congestive heart failure (CHF)
- •Has a history of acute or chronic pancreatitis
- •Has existing uncontrolled arterial hypertension (systolic blood pressure [SBP] ≥150 mmHg or diastolic blood pressure [DBP] ≥100 mmHg) despite appropriate medical therapy
- •Has a history of thromboembolic or cerebrovascular events within 6 months prior to registration
- •Has neuromuscular disorders associated with an elevated creatine kinase
- •A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment
- •Potential Participants for Cohorts A, C or E who are to Receive Binimetinib:
- •Has a history of, or current, retinal vein occlusion (RVO) or current risk factors for RVO
- •Has retinal degenerative disease
- •Potential Participants for Cohorts A, C, D or E:
- •Has a known history of Gilbert's Syndrome
- •Potential Participants for Cohorts D or E:
- •Has a previous treatment with irinotecan
- •Has plans to use, or is using, any herbal medications/supplements or any medications or foods that are strong inhibitors or inducers of cytochrome P450 3A 4/5 ≤1 week prior to the start of study treatment
研究组 & 干预措施
Cohort A Part 1: Pembrolizumab +Binimetinib 30 mg
Participants in Cohort A will receive pembrolizumab (200 mg) intravenous (IV) every 3 weeks (Q3W) plus binimetinib orally at of 30 mg twice a day (BID) until disease progression or discontinuation.
干预措施: Pembrolizumab (Biological)
Cohort A Part 1: Pembrolizumab +Binimetinib 30 mg
Participants in Cohort A will receive pembrolizumab (200 mg) intravenous (IV) every 3 weeks (Q3W) plus binimetinib orally at of 30 mg twice a day (BID) until disease progression or discontinuation.
干预措施: Binimetinib (Drug)
Cohort A Part 1: Pembrolizumab +Binimetinib 45 mg
Participants in Cohort A will receive pembrolizumab (200 mg) IV Q3W plus binimetinib orally at 45 mg BID (Dose Level 2 [DL2]) until disease progression or discontinuation.
干预措施: Pembrolizumab (Biological)
Cohort A Part 1: Pembrolizumab +Binimetinib 45 mg
Participants in Cohort A will receive pembrolizumab (200 mg) IV Q3W plus binimetinib orally at 45 mg BID (Dose Level 2 [DL2]) until disease progression or discontinuation.
干预措施: Binimetinib (Drug)
Cohort B Part 1: Pembrolizumab + mFOLFOX7
Participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W until disease progression or discontinuation.
干预措施: Pembrolizumab (Biological)
Cohort B Part 1: Pembrolizumab + mFOLFOX7
Participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W until disease progression or discontinuation.
干预措施: Oxaliplatin (Drug)
Cohort B Part 1: Pembrolizumab + mFOLFOX7
Participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W until disease progression or discontinuation.
干预措施: Leucovorin (Drug)
Cohort B Part 1: Pembrolizumab + mFOLFOX7
Participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W until disease progression or discontinuation.
干预措施: 5-Fluorouracil [5-FU] (Drug)
Cohort B Part 2: Pembrolizumab + mFOLFOX
During Part 2, participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W until disease progression or discontinuation.
干预措施: Pembrolizumab (Biological)
Cohort B Part 2: Pembrolizumab + mFOLFOX
During Part 2, participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W until disease progression or discontinuation.
干预措施: Oxaliplatin (Drug)
Cohort B Part 2: Pembrolizumab + mFOLFOX
During Part 2, participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W until disease progression or discontinuation.
干预措施: Leucovorin (Drug)
Cohort B Part 2: Pembrolizumab + mFOLFOX
During Part 2, participants in Cohort B will receive pembrolizumab (200 mg) IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W until disease progression or discontinuation.
干预措施: 5-Fluorouracil [5-FU] (Drug)
Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg
Participants in Cohort C will receive pembrolizumab 200 mg IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation.
干预措施: Pembrolizumab (Biological)
Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg
Participants in Cohort C will receive pembrolizumab 200 mg IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation.
干预措施: Binimetinib (Drug)
Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg
Participants in Cohort C will receive pembrolizumab 200 mg IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation.
干预措施: Oxaliplatin (Drug)
Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg
Participants in Cohort C will receive pembrolizumab 200 mg IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation.
干预措施: Leucovorin (Drug)
Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg
Participants in Cohort C will receive pembrolizumab 200 mg IV Q3W plus mFOLFOX7 (oxaliplatin 85mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; fluorouracil [5-FU] 2400 mg/m^2 over 46-48 hours) IV Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation.
干预措施: 5-Fluorouracil [5-FU] (Drug)
Cohort D Part 1: Pembrolizumab + FOLFIRI
Participants in Cohort D will receive a standard dose (DL1) of pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) IV Q2W until disease progression or discontinuation.
干预措施: Pembrolizumab (Biological)
Cohort D Part 1: Pembrolizumab + FOLFIRI
Participants in Cohort D will receive a standard dose (DL1) of pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) IV Q2W until disease progression or discontinuation.
干预措施: Leucovorin (Drug)
Cohort D Part 1: Pembrolizumab + FOLFIRI
Participants in Cohort D will receive a standard dose (DL1) of pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) IV Q2W until disease progression or discontinuation.
干预措施: 5-Fluorouracil [5-FU] (Drug)
Cohort D Part 1: Pembrolizumab + FOLFIRI
Participants in Cohort D will receive a standard dose (DL1) of pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) IV Q2W until disease progression or discontinuation.
干预措施: Irinotecan (Drug)
Cohort D Part 2: Pembrolizumab + FOLFIRI
During Part 2, participants in Cohort D will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) until disease progression or discontinuation.
干预措施: Pembrolizumab (Biological)
Cohort D Part 2: Pembrolizumab + FOLFIRI
During Part 2, participants in Cohort D will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) until disease progression or discontinuation.
干预措施: Leucovorin (Drug)
Cohort D Part 2: Pembrolizumab + FOLFIRI
During Part 2, participants in Cohort D will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) until disease progression or discontinuation.
干预措施: 5-Fluorouracil [5-FU] (Drug)
Cohort D Part 2: Pembrolizumab + FOLFIRI
During Part 2, participants in Cohort D will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) until disease progression or discontinuation.
干预措施: Irinotecan (Drug)
Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg
Participants in Cohort E will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation.
干预措施: Pembrolizumab (Biological)
Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg
Participants in Cohort E will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation.
干预措施: Binimetinib (Drug)
Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg
Participants in Cohort E will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation.
干预措施: Leucovorin (Drug)
Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg
Participants in Cohort E will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation.
干预措施: 5-Fluorouracil [5-FU] (Drug)
Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg
Participants in Cohort E will receive pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W in combination with binimetinib orally at a starting dose of 30 mg BID until disease progression or discontinuation.
干预措施: Irinotecan (Drug)
Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg
During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort A During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation.
干预措施: Pembrolizumab (Biological)
Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg
During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort A During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation.
干预措施: Binimetinib (Drug)
Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg
During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort A During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation.
干预措施: Leucovorin (Drug)
Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg
During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort A During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation.
干预措施: 5-Fluorouracil [5-FU] (Drug)
Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg
During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation. Cohort A During Part 2, participants in Cohort E received pembrolizumab 200 mg IV Q3W plus FOLFIRI (irinotecan 180 mg/m^2; leucovorin [calcium folinate] 400 mg/m^2; 5-FU 2400 mg/m^2 over 46-48 hours) Q2W plus binimetinib orally at the starting dose of 45 mg BID until disease progression or discontinuation.
干预措施: Irinotecan (Drug)
结局指标
主要结局
Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT)
时间窗: Up to approximately first 28 days of treatment
The occurrence of any of the following toxicities during Part 1 of the study (the first 21 days for Cohort A, first 28 days for Cohorts B,C, D, \& E), if possibly, probably or definitely related to study treatment, was considered a DLT: Grade (Gr) 4 non hematologic toxicity, Gr 4 hematologic toxicity lasting \>7 days, Gr 3 thrombocytopenia, Any non-hematologic AE ≥Gr 3 in severity, Any Gr 3 or Gr 4 non-hematologic laboratory value, Febrile neutropenia Gr 3 or Gr 4, Any prolonged delay in initiating study therapy due to a treatment-related AE that started during the DLT period, Any treatment-related toxicity that causes the participant to discontinue treatment during the DLT period, Missing \>25% of binimetinib doses as a result of drug-related AE(s), Gr 5 toxicity, Cardiac disorders and vascular disorders, Eye disorders (Retinopathy or retinal detachment Gr ≥ 3).
次要结局
- Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)(Up to Approximately 64 months)