A Randomized, Open-label Phase 3 Study of Amivantamab + FOLFIRI Versus Cetuximab/Bevacizumab + FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Recurrent, Unresectable or Metastatic Colorectal Cancer Who Have Received Prior Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 700
- 试验地点
- 253
- 主要终点
- Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
研究概览
简要总结
The purpose of this study is to compare how long the participants are disease-free (progression-free survival) and and the length of time until a participant dies (overall survival), when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus either cetuximab or bevacizumab and FOLFIRI given to participants with Kirsten rat sarcoma viral oncogene/ neuroblastoma RAS viral oncogene homolog (KRAS/ NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type recurrent, unresectable or metastatic colorectal cancer who have previously received 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
- All
- 接受健康志愿者
- 否
入选标准
- •Have histologically or cytologically confirmed adenocarcinoma of the colon or rectum. Participants must have recurrent, unresectable or metastatic disease
- •Determined to have kirsten rat sarcoma viral oncogene/neuroblastoma RAS viral oncogene homolog (KRAS/NRAS), G12, G13 and v-raf murine sarcoma viral oncogene homolog B (BRAF) V600X (X represents any single amino acid change from the original amino acid) wild type status by local and/or central next-generation sequencing (NGS) testing
- •Must agree to the submission of fresh or archival tumor tissue post progression from the most recent therapy, if clinically feasible
- •Have measurable disease according to response evaluation criteria in solid tumors (RECIST) version (v) 1.1
- •Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
- •Participant must have received 1 line of systemic therapy (fluoropyrimidine-based and oxaliplatin-based) for metastatic colorectal cancer (mCRC), with documented radiographic disease progression on or after this line of therapy. Participants can receive anti-VEGF as prior line of therapy
排除标准
- •Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
- •Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: amivantamab, cetuximab or bevacizumab or any component of FOLFIRI
- •Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
- •Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status who has not received immunotherapy treatments
- •Participant with known human epidermal growth factor receptor 2 (HER2)- positive/amplified tumor
- •Has prior exposure to irinotecan, any agents that target epidermal growth factor receptor (EGFR) or mesenchymal epithelial transition (MET)
研究组 & 干预措施
Arm B: Cetuximab or Bevacizumab + FOLFIRI
Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.
干预措施: 5-fluorouracil (Drug)
Arm B: Cetuximab or Bevacizumab + FOLFIRI
Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.
干预措施: Irinotecan (Drug)
Arm A: Amivantamab + FOLFIRI
Participants will receive amivantamab along with FOLFIRI (consisting of 5-fluorouracil, leucovorin calcium [folinic acid] or levoleucovorin, and irinotecan) as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.
干预措施: Amivantamab (Biological)
Arm B: Cetuximab or Bevacizumab + FOLFIRI
Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.
干预措施: Cetuximab (Biological)
Arm A: Amivantamab + FOLFIRI
Participants will receive amivantamab along with FOLFIRI (consisting of 5-fluorouracil, leucovorin calcium [folinic acid] or levoleucovorin, and irinotecan) as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.
干预措施: Leucovorin calcium/Levoleucovorin (Drug)
Arm B: Cetuximab or Bevacizumab + FOLFIRI
Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.
干预措施: Bevacizumab (Biological)
Arm A: Amivantamab + FOLFIRI
Participants will receive amivantamab along with FOLFIRI (consisting of 5-fluorouracil, leucovorin calcium [folinic acid] or levoleucovorin, and irinotecan) as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.
干预措施: 5-fluorouracil (Drug)
Arm B: Cetuximab or Bevacizumab + FOLFIRI
Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.
干预措施: Leucovorin calcium/Levoleucovorin (Drug)
Arm A: Amivantamab + FOLFIRI
Participants will receive amivantamab along with FOLFIRI (consisting of 5-fluorouracil, leucovorin calcium [folinic acid] or levoleucovorin, and irinotecan) as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.
干预措施: Irinotecan (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
时间窗: Up to 2 years 1 month
PFS is defined as the time from randomization until the date of objective disease progression or death (due to any cause), whichever comes first, as assessed by BICR using response evaluation criteria in solid tumors (RECIST) version (v)1.1. Participants who have not progressed or have not died at the time of analysis will be censored at their last evaluable RECIST v1.1 assessment date.
Overall Survival (OS)
时间窗: Up to 4 years 4 months
OS is defined as the time from the date of randomization to the date of participant's death due to any cause.
次要结局
- Duration of Response (DoR) as Assessed by BICR(Up to 4 years 4 months)
- Disease Control Rate as Assessed by Investigator(Up to 4 years 4 months)
- Number of Participants with Abnormalities in Laboratory Values(Up to 4 years 4 months)
- Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C30(Up to 4 years 4 months)
- Objective Response Rate (ORR) as Assessed by BICR(Up to 4 years 4 months)
- Progression Free Survival as Assessed by Investigator(Up to 4 years 4 months)
- Duration of Response as Assessed by Investigator(Up to 4 years 4 months)
- Progression Free Survival After Subsequent Therapy (PFS2)(Up to 4 years 4 months)
- Disease Control Rate (DCR) as Assessed by BICR(Up to 4 years 4 months)
- Time to Treatment Failure(Up to 4 years 4 months)
- Curative Resection (R0) Rate(Up to 4 years 4 months)
- Number of Participants with Adverse Events (AEs) by Severity(Up to 4 years 4 months)
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score(From baseline up to 4 years 4 months)
- Overall Side Effect Burden as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Item 168 Scale Score(Up to 4 years 4 months)
- ORR as Assessed by Investigator(Up to 4 years 4 months)
- Time to Response (TTR) as Assessed by BICR(Up to 4 years 4 months)
- TTR as Assessed by Investigator(Up to 4 years 4 months)
- Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-CR29) Score(From baseline up to 4 years 4 months)
- Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-CR29 Score(Up to 4 years 4 months)
- Objective Response Rate (ORR) as Assessed by BICR(Up to 4 years 4 months)
- Progression Free Survival as Assessed by Investigator(Up to 4 years 4 months)
- Objective Response Rate as Assessed by Investigator(Up to 4 years 4 months)
- Duration of Response (DoR) as Assessed by BICR(Up to 4 years 4 months)
- Duration of Response as Assessed by Investigator(Up to 4 years 4 months)
- Progression Free Survival After Subsequent Therapy (PFS2)(Up to 4 years 4 months)
- Disease Control Rate (DCR) as Assessed by BICR(Up to 4 years 4 months)
- Disease Control Rate as Assessed by Investigator(Up to 4 years 4 months)
- Time to Treatment Failure(Up to 4 years 4 months)
- Curative Resection (R0) Rate(Up to 4 years 4 months)
- Number of Participants with Adverse Events (AEs) by Severity(Up to 4 years 4 months)
- Number of Participants with Abnormalities in Laboratory Values(Up to 4 years 4 months)
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score(From baseline up to 4 years 4 months)
- Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C30(Up to 4 years 4 months)
- Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C29) Score(From baseline up to 4 years 4 months)
- Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C29 Score(Up to 4 years 4 months)
- Overall Side Effect Burden as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Item 168 Scale Score(Up to 4 years 4 months)