A Randomized, Open-label, Phase 3 Trial of Petosemtamab + FOLFIRI/mFOLFOX6 Versus Cetuximab or Bevacizumab + FOLFIRI/mFOLFOX6 as Second-line Treatment in Participants With RAS and BRAF Wild-type, Recurrent, Unresectable or Metastatic Colorectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Genmab
- 入组人数
- 600
- 主要终点
- Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Central Review (BICR)
研究概览
简要总结
The purpose of this trial is to evaluate how well petosemtamab in combination with chemotherapy works against colorectal cancer that has recurred after previous treatment and that cannot be safely removed by surgery or has spread to other parts of the body.
Participants will receive either petosemtamab + doctor's choice of chemotherapy (mFOLFOX6 or FOLFIRI) or doctor's choice of standard-of-care (SOC) cetuximab or bevacizumab + chemotherapy (mFOLFOX6 or FOLFIRI). No participants will be given placebo.
The treatment duration will be different for every participant. If a participant's cancer stays the same or gets better, and there are not any serious problems, participants can keep getting study treatment for as long as the study is open.
Participants will be asked to attend 2 visits at the study clinic for each cycle (duration of cycle is 4 weeks). During visits, there will be various tests (such as blood draws) and procedures (such as imaging) to monitor whether the study treatment is safe and effective.
The overall study duration (including screening, treatment, and follow-up) will be different for every participant.
详细描述
This is a Phase 3, randomized, open-label, global, multicenter, interventional trial to evaluate the efficacy and safety of petosemtamab in combination with investigator's choice (IC) chemotherapy (fluorouracil + leucovorin [calcium folinate] + irinotecan [FOLFIRI] or 5-FU, leucovorin [calcium folinate], and oxaliplatin [mFOLFOX6]; Arm A) versus IC cetuximab or bevacizumab in combination with IC chemotherapy (FOLFIRI or mFOLFOX6; Arm B) as second line (2L) treatment for participants with KRAS, NRAS, and BRAF wild type (wt), recurrent, unresectable or metastatic colorectal cancer (CRC).
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
- •Histologically or cytologically confirmed colorectal adenocarcinoma that is recurrent, unresectable or metastatic.
- •Must have documented KRAS and NRAS wt CRC, as determined by medical record of results from local testing or as assessed by central testing. Next-generation sequencing-based test results from tumor tissue are required for determining eligibility. At a minimum, local testing must have assessed the mutational status of KRAS and NRAS G12/G13, A59, Q61, K117, and A146 codons.
- •Has received no more than 1 line of prior systemic therapy for unresectable or metastatic CRC, with documented disease progression. First line (1L) regimen must be fluoropyrimidine- and oxaliplatin- (if 2L choice of backbone is FOLFIRI) or irinotecan- (if 2L choice of backbone is fluorouracil + leucovorin (calcium folinate) + oxaliplatin [FOLFOX]) based. Prior anti-vascular endothelial growth factor receptor (VEGF) treatment is allowed.
- •Must be eligible for treatment with mFOLFOX6 (if assigned by the investigator to receive mFOLFOX6) or FOLFIRI (if assigned by the investigator to receive FOLFIRI) according to local regulatory approvals and standard of care (SOC) guidelines.
排除标准
- •BRAF V600 mutation (eg, V600E) and/or microsatellite instability-high/deficient mismatch repair tumor status and/or ERBB2/human epidermal growth factor receptor 2 (HER2) positive/amplified tumor status as documented by local test results in the medical record or from central testing or known documented activating HRAS mutation identified prior to enrollment from local testing results in the medical record, if available .
- •Prior exposure to any agents that target epidermal growth factor receptor (EGFR) (including but not limited to protein products, monoclonal antibodies, tyrosine kinase inhibitors, or antisense oligonucleotide therapy).
- •Prior exposure to irinotecan (for participants assigned to FOLFIRI) or oxaliplatin (for participants assigned to FOLFOX) in the metastatic setting.
- •Known complete dihydropyrimidine dehydrogenase (DPD) deficiency or known homozygous/compound heterozygous dihydropyrimidine dehydrogenase gene (DPYD) variants associated with complete loss of DPD activity. Testing for DPD deficiency should be performed per local guidelines.
- •For a participant who is to receive FOLFIRI: known to be homozygous for the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1)*28 or *6 alleles or compound or double heterozygous for the UGT1A1*28 and *6 alleles. Testing for UGT1A1 should be done in accordance with local guidelines.
- •Participants with non-colorectal adenocarcinumatous disease.
- •Note: Other protocol-defined Inclusion and Exclusion criteria may apply.
研究组 & 干预措施
Arm A: Petosemtamab + IC Chemotherapy (FOLFIRI or mFOLFOX6)
Participants will receive petosemtamab 1500 milligrams (mg) once every 2 weeks (Q2W) + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.
干预措施: Petosemtamab (Drug)
Arm A: Petosemtamab + IC Chemotherapy (FOLFIRI or mFOLFOX6)
Participants will receive petosemtamab 1500 milligrams (mg) once every 2 weeks (Q2W) + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.
干预措施: Leucovorin (Calcium Folinate) (Drug)
Arm A: Petosemtamab + IC Chemotherapy (FOLFIRI or mFOLFOX6)
Participants will receive petosemtamab 1500 milligrams (mg) once every 2 weeks (Q2W) + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.
干预措施: Oxaliplatin (Drug)
Arm A: Petosemtamab + IC Chemotherapy (FOLFIRI or mFOLFOX6)
Participants will receive petosemtamab 1500 milligrams (mg) once every 2 weeks (Q2W) + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.
干预措施: Irinotecan (Drug)
Arm B: IC Cetuximab or Bevacizumab + IC Chemotherapy (FOLFIRI or mFOLFOX6)
Participants will receive IC cetuximab 500 milligrams per meter squared (mg/m^2) or bevacizumab 5 milligrams per kilogram (mg/kg) Q2W + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.
干预措施: Bevacizumab (Drug)
Arm B: IC Cetuximab or Bevacizumab + IC Chemotherapy (FOLFIRI or mFOLFOX6)
Participants will receive IC cetuximab 500 milligrams per meter squared (mg/m^2) or bevacizumab 5 milligrams per kilogram (mg/kg) Q2W + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.
干预措施: Cetuximab (Drug)
Arm B: IC Cetuximab or Bevacizumab + IC Chemotherapy (FOLFIRI or mFOLFOX6)
Participants will receive IC cetuximab 500 milligrams per meter squared (mg/m^2) or bevacizumab 5 milligrams per kilogram (mg/kg) Q2W + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.
干预措施: Leucovorin (Calcium Folinate) (Drug)
Arm A: Petosemtamab + IC Chemotherapy (FOLFIRI or mFOLFOX6)
Participants will receive petosemtamab 1500 milligrams (mg) once every 2 weeks (Q2W) + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.
干预措施: 5-FU (Drug)
Arm B: IC Cetuximab or Bevacizumab + IC Chemotherapy (FOLFIRI or mFOLFOX6)
Participants will receive IC cetuximab 500 milligrams per meter squared (mg/m^2) or bevacizumab 5 milligrams per kilogram (mg/kg) Q2W + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.
干预措施: 5-FU (Drug)
Arm B: IC Cetuximab or Bevacizumab + IC Chemotherapy (FOLFIRI or mFOLFOX6)
Participants will receive IC cetuximab 500 milligrams per meter squared (mg/m^2) or bevacizumab 5 milligrams per kilogram (mg/kg) Q2W + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.
干预措施: Oxaliplatin (Drug)
Arm B: IC Cetuximab or Bevacizumab + IC Chemotherapy (FOLFIRI or mFOLFOX6)
Participants will receive IC cetuximab 500 milligrams per meter squared (mg/m^2) or bevacizumab 5 milligrams per kilogram (mg/kg) Q2W + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.
干预措施: Irinotecan (Drug)
结局指标
主要结局
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Central Review (BICR)
时间窗: Up to approximately 2.5 years
Objective Response Rate (ORR) per RECIST v1.1 as Assessed by BICR
时间窗: Up to approximately 2.5 years
次要结局
- Curative Resection (R0) Rate(Up to approximately 3.5 years)
- Overall Survival (OS)(Up to approximately 3.5 years)
- Duration of Response (DOR) per RECIST v1.1 as Assessed by BICR(Up to approximately 3.5 years)
- Disease Control Rate (DCR) per RECIST v1.1 as Assessed by BICR(Up to approximately 3.5 years)
- Progression-free Survival after First Subsequent Therapy (PFS2)(Up to approximately 3.5 years)
- Number of Participants with Treatment-emergent Adverse Events (TEAEs)(Up to approximately 3.5 years)
- Change from Baseline in Symptoms and Functioning, as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life Questionnaire (QLQ)-F17(Baseline up to approximately 3.5 years)
- Change from Baseline in Symptoms and Functioning, as Measured by EORTC QLQ-CR29(Baseline up to approximately 3.5 years)
- Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-F17(Baseline up to approximately 3.5 years)
- Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-CR29(Baseline up to approximately 3.5 years)
- Overall Side Effect Burden, as Measured by EORTC Item 168(Baseline up to approximately 3.5 years)