A Randomized, Open-label Phase 3 Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,000
- 试验地点
- 408
- 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) when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, oxaliplatin (mFOLFOX6) or 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus cetuximab and mFOLFOX6 or FOLFIRI in adult participants with Kirsten rat sarcoma viral oncogene homolog (KRAS)/ Neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) wild type (WT) unresectable or metastatic left-sided colorectal cancer.
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 left-sided colorectal cancer. Participants must have unresectable or metastatic disease
- •Determined to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor by local and/or central testing (if available)
- •Must agree to the submission of fresh tumor tissue
- •Have measurable disease according to RECIST v1.1
- •Has not received any prior systemic therapy for unresectable or metastatic colorectal cancer (CRC). Prior adjuvant/neoadjuvant therapy in the non-metastatic disease is permitted. However, the last course of adjuvant or neoadjuvant chemotherapy must have concluded greater than (>) 12 months prior to CRC recurrence/metastases
- •Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
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: (a) amivantamab or cetuximab, (b) any component of mFOLFOX6 and, (c) 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 and human epidermal growth factor receptor 2 (HER2)-positive/amplified tumor
- •Has prior exposure to any agents that target epidermal growth factor receptor (EGFR), mesenchymal epithelial transition (MET) or vascular endothelial growth factor (VEGF)
研究组 & 干预措施
Arm A: Amivantamab in Combination With Chemotherapy
Participants will receive amivantamab in combination with chemotherapy (mFOLFOX6 [chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and oxaliplatin] or FOLFIRI [chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride]) 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 in Combination With Chemotherapy
Participants will receive cetuximab in combination with chemotherapy (mFOLFOX6 or FOLFIRI) 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 in Combination With Chemotherapy
Participants will receive amivantamab in combination with chemotherapy (mFOLFOX6 [chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and oxaliplatin] or FOLFIRI [chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride]) 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 A: Amivantamab in Combination With Chemotherapy
Participants will receive amivantamab in combination with chemotherapy (mFOLFOX6 [chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and oxaliplatin] or FOLFIRI [chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride]) 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 A: Amivantamab in Combination With Chemotherapy
Participants will receive amivantamab in combination with chemotherapy (mFOLFOX6 [chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and oxaliplatin] or FOLFIRI [chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride]) 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 Hydrochloride (Drug)
Arm A: Amivantamab in Combination With Chemotherapy
Participants will receive amivantamab in combination with chemotherapy (mFOLFOX6 [chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and oxaliplatin] or FOLFIRI [chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride]) 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: Oxaliplatin (Drug)
Arm B: Cetuximab in Combination With Chemotherapy
Participants will receive cetuximab in combination with chemotherapy (mFOLFOX6 or FOLFIRI) 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 in Combination With Chemotherapy
Participants will receive cetuximab in combination with chemotherapy (mFOLFOX6 or FOLFIRI) 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 Hydrochloride (Drug)
Arm B: Cetuximab in Combination With Chemotherapy
Participants will receive cetuximab in combination with chemotherapy (mFOLFOX6 or FOLFIRI) 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: Oxaliplatin (Drug)
Arm B: Cetuximab in Combination With Chemotherapy
Participants will receive cetuximab in combination with chemotherapy (mFOLFOX6 or FOLFIRI) 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)
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 4 years and 2 months
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.
次要结局
- Overall Survival (OS)(Up to 7 Years 3 Months)
- Objective Response Rate (ORR) as Assessed by BICR(Up to 7 Years 3 Months)
- Progression Free Survival (PFS) as Assessed by Investigator(Up to 7 Years 3 Months)
- Objective Response Rate (ORR) as Assessed by Investigator(Up to 7 Years 3 Months)
- Duration of Response (DOR) as Assessed Investigator(Up to 7 Years 3 Months)
- Progression-free Survival After Subsequent Therapy (PFS2)(Up to 7 Years 3 Months)
- Disease Control Rate (DCR) as Assessed by BICR(Up to 7 Years 3 Months)
- Time to Treatment Failure(Up to 7 Years 3 Months)
- Number of Participants with Adverse Events (AEs) by Severity(Up to 7 Years 3 Months)
- Number of Participants with Abnormalities in Laboratory Values(Up to 7 Years 3 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 7 Years 3 Months)
- Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C30(Up to 7 Years 3 Months)
- Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-CR29(Up to 7 Years 3 Months)
- Time to Response (TTR) as Assessed by BICR(Up to 7 Years 3 Months)
- Time to Response as Assessed by Investigator(Up to 7 Years 3 Months)
- Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal Cancer Module 29 (EORTC-QLQ-C29) Score(From Baseline up to 7 Years 3 Months)
- Overall Survival (OS)(Up to 7 Years 3 Months)
- Objective Response Rate (ORR) as Assessed by BICR(Up to 7 Years 3 Months)
- Progression Free Survival (PFS) as Assessed by Investigator(Up to 7 Years 3 Months)
- Objective Response Rate (ORR) as Assessed by Investigator(Up to 7 Years 3 Months)
- Duration of Response (DOR) as Assessed by BICR(Up to 7 Years 3 Months)
- Duration of Response (DOR) as Assessed Investigator(Up to 7 Years 3 Months)
- Progression-free Survival After Subsequent Therapy (PFS2)(Up to 7 Years 3 Months)
- Disease Control Rate (DCR) as Assessed by BICR(Up to 7 Years 3 Months)
- Disease Control Rate (DCR) as Assessed by Investigator(Up to 7 Years 3 Months)
- Time to Treatment Failure(Up to 7 Years 3 Months)
- Curative Resection (R0) Rate(Up to 7 Years 3 Months)
- Number of Participants with Adverse Events (AEs) by Severity(Up to 7 Years 3 Months)
- Number of Participants with Abnormalities in Laboratory Values(Up to 7 Years 3 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 7 Years 3 Months)
- Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C30(Up to 7 Years 3 Months)
- Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal Cancer Module 29 (EORTC-QLQ-C30) Score(From Baseline up to 7 Years 3 Months)
- Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-CR29(Up to 7 Years 3 Months)
- Overall Side Effect Burden as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Item 168 Scale Score(Up to 7 Years 3 Months)