Open-label, Phase 2 Study of Tusamitamab Ravtansine (SAR408701) Combined With Pembrolizumab and Tusamitamab Ravtansine (SAR408701) Combined With Pembrolizumab and Platinum-based Chemotherapy With or Without Pemetrexed in Patients With CEACAM5 Positive Expression Advanced/Metastatic Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 57
- 试验地点
- 22
- 主要终点
- All Cohorts: Number of Participants With Study Drug-Related Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
Primary Objective:
- Safety run-in part: to assess the tolerability and to determine the recommended doses of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy with or without pemetrexed to be tested in the expansion part of the study in the NSQ NSCLC population
- Expansion part (including participants treated at the recommended dose for expansion [RDE] from the Safety Run-in part): to assess the antitumor activity of several dose levels (DLs; if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population
Secondary Objectives:
- To assess the safety and tolerability of several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, and platinum-based chemotherapy with pemetrexed in the NSQ NSCLC population
- To assess the antitumor activity of several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population
- To assess the durability of the response to treatment with several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population
- To assess the antitumor activity of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy in the NSQ NSCLC population
- To assess the pharmacokinetics (PK) of tusamitamab ravtansine, pembrolizumab, pemetrexed, cisplatin, and carboplatin, each when given in combination as a doublet (tusamitamab ravtansine + pembrolizumab) or a triplet (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy) or a quadruplet (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy + pemetrexed)
- To assess the immunogenicity of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum based chemotherapy with or without pemetrexed
详细描述
The expected duration of study intervention for participants may vary, based on disease progression date; median expected duration of study per participant is estimated at 10 months (up to 1 month for screening, a median of 6 months for treatment, a median of 1 month for EOT, and follow-up visit 90 days after the last IMP administration).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Tusamitamab ravtasine 150 mg/m^2 + Pembrolizumab
Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.
干预措施: SAR408701 (Tusamitamab ravtansine) (Drug)
Tusamitamab ravtasine 150 mg/m^2 + Pembrolizumab
Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.
干预措施: Pembrolizumab (Drug)
Tusamitamab ravtasine 170 mg/m^2 + Pembrolizumab
Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.
干预措施: SAR408701 (Tusamitamab ravtansine) (Drug)
Tusamitamab ravtasine 170 mg/m^2 + Pembrolizumab
Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.
干预措施: Pembrolizumab (Drug)
Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Carboplatin will be infused over 15 to 60 minutes immediately after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: SAR408701 (Tusamitamab ravtansine) (Drug)
Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Carboplatin will be infused over 15 to 60 minutes immediately after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Pembrolizumab (Drug)
Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Carboplatin will be infused over 15 to 60 minutes immediately after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Cisplatin (Drug)
Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Carboplatin will be infused over 15 to 60 minutes immediately after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Carboplatin (Drug)
Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Carboplatin will be infused over 15 to 60 minutes immediately after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: SAR408701 (Tusamitamab ravtansine) (Drug)
Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Carboplatin will be infused over 15 to 60 minutes immediately after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Pembrolizumab (Drug)
Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Carboplatin will be infused over 15 to 60 minutes immediately after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Cisplatin (Drug)
Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Carboplatin will be infused over 15 to 60 minutes immediately after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Carboplatin (Drug)
Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: SAR408701 (Tusamitamab ravtansine) (Drug)
Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Pembrolizumab (Drug)
Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Cisplatin (Drug)
Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Carboplatin (Drug)
Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Pemetrexed (Drug)
Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: SAR408701 (Tusamitamab ravtansine) (Drug)
Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Pembrolizumab (Drug)
Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Cisplatin (Drug)
Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Carboplatin (Drug)
Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
干预措施: Pemetrexed (Drug)
结局指标
主要结局
All Cohorts: Number of Participants With Study Drug-Related Dose-Limiting Toxicities (DLTs)
时间窗: Cycle 1 Day 1 up to Cycle 1 Day 21 (cycle duration=3 weeks)
DLTs were defined as: a) Hematological abnormalities: grade 4 neutropenia for 7 or more consecutive days, grade 3 to 4 neutropenia complicated by fever (temperature ≥38.5 degree Celsius on more than 1 occasion) or microbiologically or radiographically documented infection, grade ≥3 thrombocytopenia associated with clinically significant bleeding requiring clinical intervention; b) Non-hematological abnormalities: grade 4 non-hematologic adverse event (AE), except AE symptoms related to the underlying disease as per the Investigator's judgment, grade ≥3 keratopathy. In addition, any other AE that the recruiting Investigators and sponsor deemed to be dose-limiting, regardless of its grade, was also considered as DLT.
Doublet Cohort: Objective Response Rate (ORR)
时间窗: Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks
ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per response evaluation criteria in solid tumors (RECIST) version (v) 1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Quadruplet Cohort: Objective Response Rate
时间窗: Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 139.9 weeks
ORR was defined as the percentage of participants with a confirmed CR or PR as per RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment, approximately 162.4 weeks (doublet), 117 weeks (triplet), and 143.9 weeks (quadruplet))
- Doublet and Quadruplet Cohorts: Progression-free Survival (PFS)(Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks (doublet) and 139.9 weeks (quadruplet))
- All Cohorts: Disease Control Rate (DCR)(Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks (doublet), 113 weeks (triplet), and 139.9 weeks (quadruplet))
- All Cohorts: Duration of Response (DOR)(Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks (doublet), 113 weeks (triplet), and 139.9 weeks (quadruplet))
- All Cohorts: Ctrough of Pembrolizumab(Pre-dose on Day 1 of Cycle 2 (cycle duration=3 weeks))
- Triplet Cohort: Objective Response Rate(Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 113 weeks)
- All Cohorts: Trough Concentration (Ctrough) of Tusamitamab Ravtansine(Pre-dose on Day 1 of Cycle 2 (cycle duration=3 weeks))
- Quadruplet Cohort: Plasma Concentration of Pemetrexed(30 minutes post-dose on Day 1 of Cycle 1 (cycle duration=3 weeks))
- Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion (Ceoi) of Cisplatin(At end of infusion on Day 1 of Cycle 1 (cycle duration=3 weeks))
- Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion of Carboplatin(At end of infusion on Day 1 of Cycle 1 (cycle duration=3 weeks))
- All Cohorts: Number of Participants With Treatment-emergent Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine(From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment, approximately 162.4 weeks (doublet), 117 weeks (triplet), and 143.9 weeks (quadruplet))