Pfizer's Braftovi has recently announced positive results from its phase 3 BREAKWATER trial, representing a potential milestone in the field of oncology. This study has showcased the effectiveness and safety of Braftovi (encorafenib) in combination with cetuximab (marketed as ERBITUX® ) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) in patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation. These findings have the potential to transform treatment options for individuals who have not experienced positive outcomes with conventional therapies. The results from this trial suggest that Pfizer's Braftovi could be a game-changer in managing this aggressive form of cancer.

This innovative therapy could become the standard of care for those grappling with advanced colorectal cancer, leading to enhanced clinical results and improved quality of life for patients globally. It is for this reason that we are closely examining the phase 3 BREAKWATER trial, which aims to tackle the obstacles faced by patients with BRAF V600E-mutant mCRC.

Here is a brief overview of the study:

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

Study Details | Source

  • Sponsor: Pfizer
  • 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.
  • This study is currently enrolling participants who will receive either encorafenib plus cetuximab with chemotherapy or chemotherapy alone.
  • The study team will monitor how each participant responds to the study treatment for up to about 3 years.
  • Interventions:
    • Drug: Encorafenib
    • Drug: Cetuximab
    • Drug: Oxaliplatin
    • Drug: Irinotecan
    • Drug: Leucovorin
    • Drug: 5-FU
    • Drug: Capecitabine
    • Drug: Bevacizumab
  • Primary Outcomes Measures:
    • Safety Lead-in Study: Incidence of Dose Limiting Toxicities (DLTs)
      • Incidence of dose limiting toxicity defined as any adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring during the first 28 days of treatment
      • After 30 evaluable patients in each cohort complete 1 cycle (up to 28 days), approximately 12 months
    • Phase 3: Progression free survival, by blinded independent review
      • Progression free survival, defined as the time from the date of randomization to the earliest documented disease progression or death due to any cause: encorafenib and cetuximab + mFOLFOX6 (Arm B) vs the Control Arm (Arm C)
      • Duration of Phase 3, approximately 36 months
    • Phase 3: Objective response rate by blinded independent review
      • Objective response defined as complete response (CR), or partial response (PR) according to RECIST v1.1 based on BICR assessment, from the date of randomization until the date of the first documentation of progression of disease (PD)
      • Duration of Phase 3, approximately 23 months
    • Cohort 3: Objective response rate by blinded independent review
      • Defined as CR, or PR according to RECIST v1.1 based on BICR assessment, from the date of randomization until the date of the first documentation of PD, death or start of new anticancer therapy
      • Duration of Cohort 3, approximately 15 months.

Braftovi exhibited reductions in tumor size or complete elimination of cancer, along with promising interim analysis of overall survival rates. The safety profile of Braftovi in combination with cetuximab and mFOLFOX6 in the BREAKWATER trial was consistent with the known safety profiles of each individual agent. No new safety concerns were identified. Serious treatment-related adverse events were reported in 37.7% of patients receiving Braftovi in combination with cetuximab and mFOLFOX6, compared to 34.6% of patients receiving chemotherapy with or without bevacizumab.

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