A Phase 3, Open-Label, Randomized Study of Perioperative Dostarlimab Monotherapy versus Standard of Care in Participants with Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 711
- 试验地点
- 9
- 主要终点
- To evaluate the efficacy of perioperative dostarlimab compared with SOC in participants with untreated T4N0 or Stage III(resectable), dMMR/MSI-H colon cancer
研究概览
简要总结
Rationale:
The purpose of this study is to investigate perioperative dostarlimab monotherapy versus SOC (physician choice of adjuvant FOLFOX or CAPEOX or Watch and Wait) in untreated participants with T4N0 or Stage III mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) resectable colon cancer.
Overall Design:
This is a global, Phase 3, open-label, multicenter, randomized study designed to evaluate the effect of perioperative dostarlimab monotherapy versus SOC (physician choice of adjuvant FOLFOX or CAPEOX or Watch and Wait) in participants with previously untreated T4N0 or Stage III dMMR/MSI-H, resectable colon cancer. The primary endpoint is EFS with recurrence assessed by BICR. The secondary endpoints comprise the assessment of pathological response, OS, EFS with recurrence evaluated by local assessment, safety and tolerability, PK and immunogenicity. All primary and secondary endpoints will be analyzed in all participants randomized in the study.
Number of Participants: Approximately 711 participants will be enrolled in this study.
Independent data monitoring committee: An IDMC will provide an independent review and assessment of efficacy and safety data from the study to safeguard the interest and safety of study participants and to assess for continued benefit-risk ratio for study participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Confirmed Colon Adenocarcinoma Resectable colon adenocarcinoma clinically T4N0 or Stage 3 Radiologically evaluable disease Tumor demonstrating the presence of either -MMR status must be assessed by IHC for MMR protein expression (MLH1, 2, 6 and PMS2) MSi-H phenotype as determined by PCR or by tissue NGS, MSI-H determined by local Laboratory ECOG PS of 0 or 1 Provide tissue sample from initial diagnosis adequate organ function.
排除标准
- 未提供
结局指标
主要结局
To evaluate the efficacy of perioperative dostarlimab compared with SOC in participants with untreated T4N0 or Stage III(resectable), dMMR/MSI-H colon cancer
时间窗: EFS with recurrence assessed by BICR Where an event is defined as: | 1-Disease recurrence based on radiological assessment by BICR o Disease progression precluding surgery (local assessment). | 2-Disease recurrence based on a pathological assessment of new lesions (local assessment). | 3-Death due to any cause o Treatment-related toxicity that results in the participant not being suitable for surgery
次要结局
- To further evaluate the efficacy of perioperative dostarlimab compared with SOC in participants with untreated T4N0 or Stage III (resectable), dMMR/MSI-H colon cancer.(OS, defined as time from randomization to death from any cause)
- To evaluate the efficacy of neoadjuvant dostarlimab in participants with untreated T4N0 or Stage III (resectable), dMMR/MSI-H colon cancer(Whenever there is a Pathological response determined by local assessment.)
- To evaluate the efficacy of perioperative dostarlimab compared with SOC in participants with untreated T4N0 or Stage III (resectable), dMMR/MSI-H colon cancer(EFS event with recurrence evaluated by local assessment)
- To assess the safety & tolerability of dostarlimab compared with SOC in participants with untreated T4N0 or Stage III (resectable), dMMR/MSI-H colon cancer(Whenever there are treatment emergent AEs SAEs imAEs & AEs leading to death or discontinuation of study intervention)
- To describe the PK of dostarlimab in participants with untreated T4N0 or Stage III (resectable), dMMR/MSI-H colon cancer(Serum concentrations and relevant PK parameters (C-EoI and Ctrough) for dostarlimab)
- To determine the immunogenicity of dostarlimab in participants with untreated T4N0 or Stage III (resectable), dMMR/MSI-H colon cancer(Incidence of ADA against dostarlimab)
研究者
Dr Gaurav Deshmukh
GSK Pharma India Private Limited