A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF ENCORAFENIB AND CETUXIMAB PLUS PEMBROLIZUMAB VERSUS PEMBROLIZUMAB ALONE IN PARTICIPANTS WITH PREVIOUSLY UNTREATED BRAF V600E-MUTANT, MSI H/DMMR METASTATIC COLORECTAL CANCER
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 108
- 试验地点
- 61
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
The purpose of this study is to learn about the effects of three study medicines (encorafenib, cetuximab, and pembrolizumab) given together for the treatment of colorectal cancer that:
- is metastatic (spread to other parts of the body);
- has the condition of genetic hypermutability (tendency to mutation) or impaired DNA mismatch repair (MMR)
- has a certain type of abnormal gene called "BRAF" and;
- has not received prior treatment.
All participants in this study will receive pembrolizumab at the study clinic as an intravenous (IV) infusion (given directly into a vein) at the study clinic.
In addition, half of the participants will take encorafenib by mouth at home every day and cetuximab by IV infusion at the study clinic.
The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Locally confirmed microsatellite instability-high/ deficient mismatch repair (MSI-H/dMMR) stage IV colorectal carcinoma
- •Locally confirmed BRAF V600E mutation in tumor tissue or blood
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Have not received prior systemic regimens for metastatic disease.
- •Measurable disease per RECIST 1.1
- •Adequate organ function
排除标准
- •Colorectal adenocarcinoma that is RAS mutant or for which RAS mutation status is unknown
- •Known active central nervous system metastases and/or carcinomatous meningitis; leptomeningeal disease
- •Immunodeficiency or active autoimmune disease requiring systemic treatment in the past 2 years
- •Presence of acute or chronic pancreatitis
- •Clinically significant cardiovascular diseases (eg, thromboembolic or cerebrovascular accident events ≤ 12 wks prior)
- •Received a live or live-attenuated vaccine within 30 days of planned start of study medication
- •Previous treatment with any selective BRAF inhibitor (eg, encorafenib, dabrafenib, vemurafenib, XL281/BMS-908662) or any epidermal growth factor receptor (EGFR) inhibitor (eg, cetuximab, panitumumab).
- •Previous treatment with an immune checkpoint inhibitor (eg, anti-programmed cell death [PD-1], anti-PD-L1 or anti-PD-L2 agent); or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
研究组 & 干预措施
Arm A: encorafenib, cetuximab and pembrolizumab
Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.
干预措施: Encorafenib (Drug)
Arm A: encorafenib, cetuximab and pembrolizumab
Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.
干预措施: Cetuximab (Biological)
Arm A: encorafenib, cetuximab and pembrolizumab
Participants receive encorafenib orally + cetuximab IV + pembrolizumab IV.
干预措施: Pembrolizumab (Biological)
Arm B: pembrolizumab
Participants receive pembrolizumab IV.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Duration of study, approximately 45 months
PFS per investigator, defined as the time from randomization until PD based on investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first:
次要结局
- Incidence of adverse events(Duration of study, approximately 45 months)
- Overall Survival (OS)(Duration of study, approximately 45 months)
- Objective Response (OR)(Duration of study, approximately 45 months)