A Randomized, Open-label, Phase 3 Trial of Petosemtamab in Combination With mFOLFOX6 or FOLFIRI Versus Cetuximab in Combination With mFOLFOX6 or FOLFIRI as First-line Treatment for Participants With RAS and BRAF Wild-type, Unresectable or Metastatic, Left-sided Colorectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Genmab
- 入组人数
- 960
- 试验地点
- 6
- 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 located on the left side of the colon 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 standard-of-care cetuximab + doctor's choice of 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 Phase 3, randomized, open-label, global trial is designed to assess the efficacy and safety of petosemtamab plus investigator's choice (IC) chemotherapy (fluorouracil + leucovorin (calcium folinate) + oxaliplatin [mFOLFOX6] or fluorouracil + leucovorin (calcium folinate) + irinotecan [FOLFIRI]) versus standard of care (SOC) (ie, cetuximab + IC chemotherapy [mFOLFOX6 or FOLFIRI]) as 1L therapy in participants with 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
- •Histologically or cytologically confirmed left-sided colorectal adenocarcinoma that is unresectable or metastatic.
- •Must have documented KRAS and NRAS wild type (wt) colorectal cancer (CRC), as determined by medical record of results from local testing or as assessed by central testing. Local testing must have been conducted in accordance with local guidelines using an Food and Drug Administration (FDA)-approved test or a laboratory-developed test that is validated in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (sites in the United States) or an accredited local laboratory (sites outside of the United States). Next-generation sequencing (NGS)-based test results from tumor tissue are required for determining eligibility. Polymerase chain reaction (PCR)-based tests, sanger sequencing, or pyrosequencing test results are not allowed.
- •Has not received any prior systemic therapy for unresectable or metastatic CRC.
- •Must be eligible for treatment with mFOLFOX6 (if assigned to receive mFOLFOX6) or FOLFIRI (if assigned to receive FOLFIRI) according to local regulatory approvals and SOC guidelines.
排除标准
- •BRAF mutation, and/or microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) and/or protocol specified 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).
- •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 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 adenocarcinomatous disease.
- •Note: Other protocol-defined Inclusion and Exclusion criteria may apply.
研究组 & 干预措施
Petosemtamab + IC Chemotherapy
Participants will receive petosemtamab and IC chemotherapy (mFOLFOX6 or FOLFIRI).
干预措施: FOLFIRI (Drug)
Cetuximab + IC Chemotherapy
Participants will receive cetuximab + IC chemotherapy (mFOLFOX6 or FOLFIRI).
干预措施: mFOLFOX6 (Drug)
Cetuximab + IC Chemotherapy
Participants will receive cetuximab + IC chemotherapy (mFOLFOX6 or FOLFIRI).
干预措施: Cetuximab (Drug)
Petosemtamab + IC Chemotherapy
Participants will receive petosemtamab and IC chemotherapy (mFOLFOX6 or FOLFIRI).
干预措施: Petosemtamab (Drug)
Petosemtamab + IC Chemotherapy
Participants will receive petosemtamab and IC chemotherapy (mFOLFOX6 or FOLFIRI).
干预措施: mFOLFOX6 (Drug)
Cetuximab + IC Chemotherapy
Participants will receive cetuximab + IC chemotherapy (mFOLFOX6 or FOLFIRI).
干预措施: FOLFIRI (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 35 months
Objective Response Rate (ORR) per RECIST v1.1 as Assessed by BICR
时间窗: Up to approximately 35 months
次要结局
- Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-CR29(Up to approximately 62 months)
- Overall Side Effect Burden, as Measured by EORTC Item 168(Up to approximately 62 months)
- Change from Baseline in Symptoms and Functioning, as Measured by EORTC QLQ-CR29(Baseline up to approximately 62 months)
- Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-F17(Up to approximately 62 months)
- Duration of Response (DOR) per RECIST v1.1 as Assessed by BICR(Up to approximately 62 months)
- Disease Control Rate (DCR) per RECIST v1.1 as Assessed by BICR(Up to approximately 62 months)
- Progression-free Survival after First Subsequent Therapy (PFS2)(Up to approximately 62 months)
- Overall Survival (OS)(Up to approximately 62 months)
- Curative Resection (R0) Rate(Up to approximately 62 months)
- Number of Participants with Adverse Events (AEs)(Up to approximately 62 months)
- 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 62 months)