Mektovi (binimetinib)

The exarafenib plus binimetinib combination demonstrated superior efficacy in diverse preclinical models. This study establishes ARAF-KSR1 complex formation as a novel resistance mechanism to pan-RAF inhibition and provides mechanistic rationale for combination strategies with potential to address the unmet clinical need for BRAF Class II and III-mutated NSCLC.

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.

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.

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.

This case illustrates the potential of precision therapy in the treatment of MM with BRAFV600E mutation. Panel sequencing and minimally invasive approaches to diagnosis and disease monitoring can significantly contribute to personalized care and a better understanding of disease dynamics.

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.

Safety profile remained consistent with that in prior analyses. While comparisons across trials should be done cautiously, encorafenib plus binimetinib was associated with the the longest mOS reported to date with targeted treatment in patients with treatment-naïve BRAF V600E-mutant mNSCLC.

P1/2, N=144, Active, not recruiting, Deciphera Pharmaceuticals, LLC | Recruiting --> Active, not recruiting

This study is limited by its retrospective design and small sample size, warranting cautious interpretation of results. These findings provide supportive evidence for the use of binimetinib in patients with NRAS-mutant melanoma following immune checkpoint inhibitor failure.

P1/2, N=105, Completed, Children's Hospital Los Angeles | Active, not recruiting --> Completed | Trial completion date: Nov 2023 --> Aug 2025