Braftovi (encorafenib)

BRAF V600E is associated with inferior prognoses compared to BRAF WT in early-stage CC. This finding will help optimize trial design for this population.

P1/2, N=38, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

P2, N=24, Active, not recruiting, Providence Health & Services | Trial completion date: Oct 2027 --> Jan 2027 | Trial primary completion date: Oct 2025 --> Jan 2026

P2, N=98, Completed, Pfizer | Active, not recruiting --> Completed

A 40-year-old man diagnosed with metastatic BRAFV600E mutant sigmoid adenocarcinoma received multiple lines of treatment, including first-line chemotherapy + bevacizumab and targeted therapy of cetuximab, encorafenib ± binimetinib. This case demonstrates the potential application of ctDNA and fragmentomics biomarkers, molecular analyses, and drug testing in noninvasive therapeutic monitoring of BRAFV600E mutant mCRC. These illustrate the potential application of such noninvasive therapeutic monitoring in larger scale cohorts of patients.

The BREAKWATER Phase III study investigated encorafenib and cetuximab plus mFOLFOX6 versus chemotherapy with or without bevacizumab for the treatment of patients with previously untreated BRAF V600E - mutant metastatic colorectal cancer...This paradigm shift in metastatic colorectal cancer highlights the importance for early genomic testing to identify patients who would benefit from this new treatment option. We discuss the results from BREAKWATER - including progression-free survival by blinded independent central review, overall survival, objective response rate by blinded independent central review in all participants, and safety - and the meaning of these results for clinical practice as a new treatment option and the need for earlier genomic testing.Clinical Trial Registration: www.clinicaltrials.gov identifier is NCT04607421.

A clinical drug-drug interaction (DDI) study was designed to evaluate the effect of single and multiple oral doses of encorafenib on the single oral dose pharmacokinetics (PK) of the cytochrome P450 (CYP) enzyme probe substrates, losartan (CYP2C9), midazolam (CYP3A4), caffeine (CYP1A2), omeprazole (CYP2C19), and dextromethorphan (CYP2D6) administered as a cocktail (Inje). Based on these results regarding co-administration with encorafenib, sensitive substrates of CYP3A should be avoided or dose adjusted based on the recommendations of their approved product labeling. This information has been included in the updated prescribing information for encorafenib.

EST and Encorafenib (ECB as the internal standard) were differentiated using an isocratic mobile phase system on a reversed stationary phase (Eclipse Plus C18) column. In silico data proposed that minor structural modifications to the dichlorophenyl moiety or the piperazine ring during drug design may enhance the safety profile and metabolic stability relative to the properties of EST. Evaluating the EST metabolic stability and in silico ADME characteristics is essential for advancing innovative therapeutic research focused on improving metabolic stability.

The BEACON regimen, comprising cetuximab, encorafenib, and binimetinib, is a critical treatment for BRAF-mutant metastatic colorectal cancer (mCRC). These cases highlight the importance of early recognition and proactive management of ocular toxicity in patients receiving BEACON therapy. Regular ophthalmological monitoring and appropriate dose adjustments are essential to prevent visual damage while maintaining treatment efficacy.

P2, N=43, Recruiting, Northwestern University | Trial completion date: Jul 2025 --> Jul 2028 | Trial primary completion date: Jul 2024 --> Jul 2026

We found no evidence that encorafenib plus binimetinib is superior to dabrafenib plus trametinib in metastatic melanoma. These findings suggest that the choice between these combinations should be guided by tolerability profiles and economic considerations rather than efficacy.