Mektovi (binimetinib)

In here we report a case of a female patient who developed LMD from a Pleomorphic Xanthoastrocytoma (PXA), BRAFV600-mutated, who has shown successful response to treatment with BRAF/MEKi (Encorafinib/Binimetinib) for over 3 years since initial LMD diagnosis. The effectiveness of therapy in this patient was initially observed as stable disease, with radiographic progression when BRAF/MEKi were withheld, and immediate tumor control achieved when reinstated. Despite being just one case, this hopefully could serve as proof-of-concept for use of targeted therapy for BRAF V600E-mutated tumors with LMD progression, sparing patients from alternative tumor control options such as radiation therapy.

The patient was initially diagnosed with T4bN1bM1 and experienced disease progression following surgery and lenvatinib treatment. This possibility is supported by reliable evidence for the use of BRAF plus MEK inhibitor for brain metastasis from BRAF-mutated malignant melanoma. We conclude that encorafenib plus binimetinib treatment for brain metastasis from BRAF-mutated thyroid cancer is a safe and effective treatment choice.

P1, N=40, Recruiting, University Health Network, Toronto | Trial primary completion date: Dec 2025 --> Aug 2026

P1/2, N=75, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2025 --> Nov 2026

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.