Phase II, Open-label, Single Arm, Multicenter Study of Encorafenib, Binimetinib Plus Cetuximab in Subjects With Previously Untreated BRAF V600E -Mutant Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 95
- 试验地点
- 83
- 主要终点
- Confirmed Overall Response Rate (cORR) Based on Local Tumor Assessments
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of the combination of study drugs encorafenib, binimetinib and cetuximab in patients who have BRAF V600 mutant metastatic colorectal cancer and have not received any prior treatment for their metastatic disease.
详细描述
The presence of a BRAFV600E mutation is considered a marker of poor prognosis in subjects with mCRC. The preclinical results and preliminary clinical data together justify the evaluation of this triple combination in the first-line setting of this population. The primary objective of the study is to evaluate the antitumor activity of the combination of encorafenib, binimetinib and cetuximab by assessing the overall response rate in adult subjects with previously untreated BRAFV600E-mutant metastatic colorectal cancer. It will also assess the effect of the triple combination on the duration of response, time to response, progression-free survival and overall survival and assess the effect on quality of life. It will also characterize the safety and tolerability of the triple combination as well as describe the pharmacokinetics (PK) of encorafenib, binimetinib, and cetuximab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
All involved know the identity of the intervention assignment.
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
- •Male or female ≥ 18 years of age
- •Histologically or cytologically confirmed CRC that is metastatic
- •Presence of BRAF V600E in tumor tissue determined by local assay at any time prior to screening
- •Evidence of measurable disease as per RECIST, v1.1
- •Subject able to receive cetuximab as per approved label with regards to RAS status
- •Eastern Cooperative Oncology Group Status (ECOG) 0 or 1
- •Adequate renal, hepatic, cardiac and bone marrow functions and adequate electrolytes as per protocol
- •Subject able to take oral medications
排除标准
- •Prior systemic therapy for metastatic disease
- •Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab or other anti-EGFR inhibitors
- •Symptomatic brain metastasis or Leptomeningeal disease
- •History or current evidence of Retinal Vein Occlusion (RVO) or current risk factors for RVO
- •History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months prior to first dose.
- •Impaired cardiovascular function or clinically significant cardiovascular diseases: history of myocardial infarction or coronary disorders within 6 months prior to start of study treatment, symptomatic congestive heart failure (grade 2 or higher), past or current clinically significant arrhythmia and/or conduction disorder within 6 months prior to study treatment start
- •History of thromboembolic or cerebrovascular events within 6 months prior to start of study treatment
- •Concurrent neuromuscular disorder that is associated with potential elevation of Creatine Kinase
- •Known contraindication to cetuximab administration as per SPC/approved label
研究组 & 干预措施
1 Arm
encorafenib plus binimetinib plus cetuximab
干预措施: encorafenib (Drug)
1 Arm
encorafenib plus binimetinib plus cetuximab
干预措施: Binimetinib (Drug)
1 Arm
encorafenib plus binimetinib plus cetuximab
干预措施: Cetuximab (Drug)
结局指标
主要结局
Confirmed Overall Response Rate (cORR) Based on Local Tumor Assessments
时间窗: From initiation of treatment to disease progression up to a maximum of 17.6 months.
The confirmed overall response rate (cORR) is the percentage of confirmed responses, defined as complete response (CR) or partial response (PR), as assessed by local radiologist/investigator review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.
次要结局
- Confirmed Overall Response Rate (cORR) Based on Central Tumor Assessment(From initiation of treatment to disease progression up to a maximum of 17.6 months)
- Duration of Response (DOR) Per Central Assessment(From first radiographic evidence of response to disease progression up to a maximum of 17.6 months)
- Overall Response Rate (ORR) Based on Local Tumor Assessments(From initiation of treatment to disease progression up to a maximum of 17.6 months)
- Overall Response Rate (ORR) Based on Central Tumor Assessments(From initiation of treatment to disease progression up to a maximum of 17.6 months)
- Plasma Concentration of Encorafenib(2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days))
- Duration of Response (DOR) Per Local Assessment(From first radiographic evidence of response to disease progression up to a maximum of 17.6 months)
- Time to Response (TTR) Per Local Review(From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months)
- Time to Response (TTR) Per Central Review(From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months)
- Progression-Free Survival (PFS) Per Local Review(From initiation of treatment to disease progression or death up to a maximum of 17.6 months)
- Progression of Free Survival (PFS) Per Central Review(From initiation of treatment to disease progression or death up to a maximum of 17.6 months)
- Overall Survival (OS)(From initiation of treatment to death up to a maximum of 17.6 months)
- Plasma Concentration of Binimetinib(2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days))
- Plasma Concentration of Cetuximab(2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days))
- Change From Baseline in EORTC QLQ-C30 Over Time(From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months)
- Change From Baseline in EQ-5D-5L Over Time(From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months)
- PGIC Scores Over Time(From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months)