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.
Name: encorafenib
Name: Binimetinib
Name: Cetuximab
Description: Assessment of tumor evaluation change from baseline
Measure: Confirmed Overall Response Rate (cORR) based on local tumor assessments Time: Duration of the study, approximately 25 monthsDescription: Percentage of subjects with complete response (CR) and partial response (PR)
Measure: Confirmed Overall Response Rate (cORR) based on central tumor assessment Time: globally assessed by subject based on tumor evaluations every 6 weeks for the first 12 weeks and then every 8 weeks.Description: Percentage of subjects with complete response (CR) and partial response (PR)
Measure: Overall response (ORR) based on local tumor assessments Time: Globally assessed by subject based on tumor evaluations every 6 weeks for the first 12 weeks and then every 8 weeks.Description: Percentage of subjects with complete response (CR) and partial response (PR)
Measure: Overall response (ORR) based on central tumor assessments Time: Globally assessed by subject based on tumor evaluations every 6 weeks for the first 12 weeks and then every 8 weeks.Description: Time from first radiographic evidence of response assessed based on local radiologist/investigator review to the earliest documented PD or death due to underlying disease
Measure: Duration of Response (DOR) per local assessment Time: Duration of study approximately 25 monthsDescription: Time from first radiographic evidence of response review to the earliest documented PD or death due to underlying disease
Measure: Duration of Response (DOR) per central assessment Time: Duration of study approximately 25 monthsDescription: Time from first dose until first documented radiographic evidence of response of CR or PR
Measure: Time to Response (TTR) per local review Time: Duration of study approximately 25 monthsDescription: Time from first dose until first documented radiographic evidence of response of CR or PR
Measure: Time to Response (TTR) per central review Time: Duration of study approximately 25 monthsDescription: Time from first dose to the earliest documented date of disease progression or death due to any cause
Measure: Progression of Free Survival (PFS) per local review Time: Duration of study approximately 25 monthsDescription: Time from first dose to the earliest documented date of disease progression or death due to any cause
Measure: Progression of Free Survival (PFS) per central review Time: Duration of study approximately 25 monthsDescription: Time from first dose to death due to any cause
Measure: Overall Survival (OS) Time: Duration of study approximately 25 monthsDescription: Plasma concentration of encorafenib
Measure: Plasma concentration of encorafenib Time: 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)Description: Plasma concentration of binimetinib
Measure: Plasma concentration of binimetinib Time: 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)Description: Plasma concentration of cetuximab
Measure: Plasma concentration of cetuximab Time: 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)Description: Change in the Quality of Life Questionnaire for Cancer subjects.
Measure: Comparison of Quality of Life from Baseline to end of the study Time: At screening, at Cycle 1 Day 1 and at the end of the study (each cycle is 28 days)Allocation: N/A
Single Group Assignment
There is one SNP
Phase II, Open-label, Single Arm, Multicenter Study of Encorafenib, Binimetinib Plus Cetuximab in Subjects With Previously Untreated BRAF V600E -Mutant Metastatic Colorectal Cancer. --- V600E ---
Change in the Quality of Life Questionnaire for Cancer subjects.. Inclusion Criteria: - 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 and confirmed by central laboratory - Evidence of measurable disease as per RECIST, v1.1 - Subject able to receive cetuximab as per approved label with regards to RAS status - ECOG Status 0 or 1 - Adequate renal, hepatic, cardiac and bone marrow functions and adequate electrolytes as per protocol - Subject able to take oral medications Exclusion Criteria: - 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. --- V600E ---
- 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 Inclusion Criteria: - 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 and confirmed by central laboratory - Evidence of measurable disease as per RECIST, v1.1 - Subject able to receive cetuximab as per approved label with regards to RAS status - ECOG Status 0 or 1 - Adequate renal, hepatic, cardiac and bone marrow functions and adequate electrolytes as per protocol - Subject able to take oral medications Exclusion Criteria: - 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. --- V600E ---
- 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 BRAF V600E-mutant Metastatic Colorectal Cancer Colorectal Neoplasms The presence of a BRAFV600E mutation is considered a marker of poor prognosis in subjects with mCRC. --- V600E ---