A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer

Official Title

An open-label, multicenter, randomized phase 3 study of first-line encorafenib plus cetuximab with or without chemotherapy versus standard of care therapy with a safety lead-in of encorafenib and cetuximab plus chemotherapy in participants with metastatic braf v600e-mutant colorectal cancer

Summary:

The purpose of this study is to evaluate two study medicines (encorafenib plus cetuximab) taken alone or together with standard chemotherapy for the potential treatment of colorectal cancer that:

• has spread to other parts of the body (metastatic);
• has a certain type of abnormal gene called "BRAF"; and
• has not received prior treatment.

Participants in this study will receive one of the following study treatments:

• Encorafenib plus cetuximab: These participants will receive encorafenib by mouth at home every day and cetuximab once every two weeks by intravenous (IV) infusion (an injection into the vein) at the study clinic.
• Encorafenib plus cetuximab with chemotherapy: These participants will receive encorafenib and cetuximab in the way described in the bullet above. Additionally, they will receive standard chemotherapy by IV infusion and oral treatment at home.
• Chemotherapy alone: These participants will receive chemotherapy, the standard treatment for this condition, by IV infusion at the study clinics and oral treatment at home.

The study team will monitor how each participant responds to the study treatment for up to about 3 years.

Trial Description

Primary Outcome:

• Safety Lead-in Study: Incidence of Dose Limiting Toxicities (DLTs)
• Phase 3: Progression free survival, by blinded independent review

Secondary Outcome:

• Safety Lead-in: Incidence of adverse events
• Safety Lead-in: Incidence of abnormal clinical laboratory parameters, abnormal vital signs and abnormal electrocardiograms
• Safety Lead-in: Incidence of dose interruptions, dose modifications and discontinuations due to adverse events
• Safety Lead-in: Overall response rate by investigator
• Safety Lead-in: Duration of response by Investigator
• Safety Lead-in:Progression free survival by Investigator
• Safety Lead-in: Time to response by Investigator
• Safety Lead-in: Overall survival
• Phase 3: Overall survival and Progression free survival by blinded independent review
• Phase 3: Overall response rate by blinded independent review and by Investigator
• Phase 3: Duration of response by blinded independent review and by Investigator
• Phase 3: Time to response by blinded independent review and by Investigator
• Phase 3: Progression free survival by Investigator
• Phase 3: Progression free survival 2 by Investigator
• Phase 3: Incidence of adverse events
• Phase 3: Incidence of abnormal clinical laboratory parameters, abnormal vital signs and abnormal electrocardiograms
• Phase 3: Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30)
• Phase 3: Change from Baseline in the EuroQol-5D-5L (EQ-5D-5L) Questionnaire
• Phase 3: Change from Baseline in the Patient Global Impression of Severity (PGIS)
• Phase 3: Change from Baseline in the Patient Global Impression of Change (PGIC) questionnaires
• Phase 3: Confirm the MSI-status in tumour tissue
• Phase 3: Determine the correlation between cfDNA genetic alterations and clinical outcome
• Safety Lead-in: Maximum plasma concentration of encorafenib, LHY746, irinotecan and SN-38
• Safety Lead-in: Area under the plasma concentration time curve of encorafenib, LHY746, irinotecan and SN-38
• Safety Lead-in: Time to maximim plasma concentration time curve of encorafenib, LHY746, irinotecan and SN-38
• Safety Lead-in: Maximum plasma concentration of encorafenib, LHY746 and oxaliplatin
• Safety Lead-in: Area under the plasma concentration time curve of encorafenib, LHY746 and oxaliplatin
• Safety Lead-in: Clearance of irinotecan, SN-38 and oxaliplatin
• Safety Lead-in: Time to maximim plasma concentration time curve of encorafenib, LHY746 and oxaliplatin
• Phase 3: Trough concentrations of encorafenib and its metabolite LHY746

The purpose of the study is to evaluate whether encorafenib plus cetuximab (EC), alone or in combination with chemotherapy, can improve clinical outcomes relative to current standard of-care chemotherapy in participants with previously untreated BRAF V600E-mutant mCRC. Since encorafenib has not previously been combined with chemotherapy, the tolerability and PK of EC in combination with mFOLFOX6 and in combination with FOLFIRI will be evaluated in separate cohorts in the safety lead-in portion of the trial in order to identify which chemotherapy combination is to be used in the Phase 3 portion of the study.

View this trial on ClinicalTrials.gov