FORWARD I: A Randomized, Open Label Phase 3 Study to Evaluate the Safety and Efficacy of Mirvetuximab Soravtansine (IMGN853) Versus Investigator's Choice of Chemotherapy in Women With Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 366
- 试验地点
- 131
- 主要终点
- Progression-Free Survival (PFS), as Assessed by BIRC Per RECIST Version 1.1 in All Participants Randomized to the Study
研究概览
简要总结
This is a Phase 3, open label, randomized study designed to compare the safety and efficacy of mirvetuximab soravtansine to that of selected single-agent chemotherapy (Investigator's choice) in women with platinum-resistant FR-alpha positive advanced EOC, primary peritoneal cancer and/or fallopian tube cancer.
详细描述
Participants will be randomized to either mirvetuximab soravtansine or investigator's choice chemotherapy.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Participants must be diagnosed with advanced epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer
- •Participants must have folate receptor alpha positive tumor expression as defined in the protocol
- •Participants must have platinum-resistant ovarian cancer, defined as progression within 6 months from completion of a minimum of four cycles of platinum-containing therapy.
- •Participants must have received at least one but no more than three prior systemic treatment regimens and for whom single-agent chemotherapy is appropriate as the next line of treatment
- •Participants must have at least one lesion that meets the definition of measurable disease by RECIST 1.1
排除标准
- •Diagnosis of clear cell, low grade ovarian cancer or mixed tumors
- •Participants with primary platinum-refractory disease
- •Serious concurrent illness or clinically relevant active infection as defined in the protocol
- •Prior treatment with mirvetuximab soravtansine
- •Women who are pregnant or breast feeding
研究组 & 干预措施
Mirvetuximab Soravtansine
Participants will receive mirvetuximab soravtansine at 6 milligrams/kilogram (mg/kg) adjusted ideal body weight (AIBW) administered intravenously (IV) on Day 1 of a 3 week cycle. Participants will continue to receive study drug until they experience progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (as assessed by the blinded independent review committee [BIRC]), experience unacceptable toxicity, or withdraw consent, whichever comes first, or until the sponsor terminate the study. (Maximum exposure: 86.9 weeks)
干预措施: Mirvetuximab soravtansine (Drug)
Investigator's Choice (IC) Chemotherapy
Participants will receive a dose of IC chemotherapeutic agent calculated using body surface area (BSA). Paclitaxel will be administered at 80 milligrams/square meter (mg/m^2) as a 1-hour IV infusion on Days 1, 8, 15, and 22 of a 4-week cycle; or topotecan will be administered at 4 mg/m^2 over 30 minutes on Days 1, 8, and 15 of a 4-week cycle. Alternatively, topotecan could be administered at 1.25 mg/m^2 over 30 minutes on Days 1 to 5 of a 3-week cycle; or pegylated liposomal doxorubicin will be administered at 40 mg/m^2 as a 1 mg/minute IV infusion on Day 1 of a 4-week cycle. After Cycle 1, if tolerated, pegylated liposomal doxorubicin could be administered as a 1-hour infusion. Participants will continue to receive study drug until they experience PD per RECIST version 1.1 (as assessed by BIRC), experience unacceptable toxicity, or withdraw consent, whichever comes first, or until the sponsor terminate the study. (Maximum exposure: 62.9 weeks)
干预措施: Paclitaxel (Drug)
Investigator's Choice (IC) Chemotherapy
Participants will receive a dose of IC chemotherapeutic agent calculated using body surface area (BSA). Paclitaxel will be administered at 80 milligrams/square meter (mg/m^2) as a 1-hour IV infusion on Days 1, 8, 15, and 22 of a 4-week cycle; or topotecan will be administered at 4 mg/m^2 over 30 minutes on Days 1, 8, and 15 of a 4-week cycle. Alternatively, topotecan could be administered at 1.25 mg/m^2 over 30 minutes on Days 1 to 5 of a 3-week cycle; or pegylated liposomal doxorubicin will be administered at 40 mg/m^2 as a 1 mg/minute IV infusion on Day 1 of a 4-week cycle. After Cycle 1, if tolerated, pegylated liposomal doxorubicin could be administered as a 1-hour infusion. Participants will continue to receive study drug until they experience PD per RECIST version 1.1 (as assessed by BIRC), experience unacceptable toxicity, or withdraw consent, whichever comes first, or until the sponsor terminate the study. (Maximum exposure: 62.9 weeks)
干预措施: Pegylated liposomal doxorubicin (Drug)
Investigator's Choice (IC) Chemotherapy
Participants will receive a dose of IC chemotherapeutic agent calculated using body surface area (BSA). Paclitaxel will be administered at 80 milligrams/square meter (mg/m^2) as a 1-hour IV infusion on Days 1, 8, 15, and 22 of a 4-week cycle; or topotecan will be administered at 4 mg/m^2 over 30 minutes on Days 1, 8, and 15 of a 4-week cycle. Alternatively, topotecan could be administered at 1.25 mg/m^2 over 30 minutes on Days 1 to 5 of a 3-week cycle; or pegylated liposomal doxorubicin will be administered at 40 mg/m^2 as a 1 mg/minute IV infusion on Day 1 of a 4-week cycle. After Cycle 1, if tolerated, pegylated liposomal doxorubicin could be administered as a 1-hour infusion. Participants will continue to receive study drug until they experience PD per RECIST version 1.1 (as assessed by BIRC), experience unacceptable toxicity, or withdraw consent, whichever comes first, or until the sponsor terminate the study. (Maximum exposure: 62.9 weeks)
干预措施: Topotecan (Drug)
结局指标
主要结局
Progression-Free Survival (PFS), as Assessed by BIRC Per RECIST Version 1.1 in All Participants Randomized to the Study
时间窗: From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
PFS was defined as the time from randomization until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the sum of the longest diameters (SoD) of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
PFS, as Assessed by BIRC Per RECIST Version 1.1 in Participants With High Folate Receptor Alpha Level (≥ 75% of Tumor Staining)
时间窗: From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
PFS was defined as the time from randomization until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
次要结局
- Gynecologic Cancer Intergroup (GCIG) CA-125 Response Rate: Percentage of Participants With GCIG CA-125 Confirmed Clinical Responses(From first dose of study drug until CA-125 response (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm))
- Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by BIRC Per RECIST1.1(From randomization until first BOR of CR or PR (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm))
- Overall Survival (OS)(From the date of randomization until the time of death (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm))
- Number of Participants Achieving at Least a 15% (≥ 15-Point) Absolute Improvement From Baseline on the EORTC QLQ-OV28 Abdominal/Gastrointestinal (AB/GI) Symptom Subscale at Week 8/9 Assessment(Baseline, Week 8/9)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm))
- PFS, as Assessed by Investigator Per RECIST Version 1.1(From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm))
- Duration of Response (DOR), as Assessed by BIRC Per RECIST v1.1(From the date of first response (CR or PR) until the date of PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm))
- Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4(Pre-dose and within 5 minutes after mirvetuximab soravtansine infusion on Day 1 of Cycles 1 and 3; and Day 8 and 15 of Cycles 1 and 3)
- Number of Participants With Anti-Drug Antibodies (ADA)(Pre-dose and within 5 minutes after mirvetuximab soravtansine infusion on Day 1 of Cycles 1, 2, and 4; pre-dose on Day 1 of Cycle 6)