Mektovi (binimetinib)

Encorafenib, cetuximab, and binimetinib are targeted therapies developed for metastatic colorectal cancer with a BRAF V600E mutation. The case highlights the potential use of BRAF V600E targeted therapy in BRAF V600E-mutated duodenal cancer and the importance of molecular profiling in rare cancers. Further research is needed on the effect and safety of targeted therapy for small bowel adenocarcinoma.

P2, N=66, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> May 2026 | Trial primary completion date: Jan 2026 --> May 2026

The oral drug combination was well tolerated with no dose-limiting toxicity or need for dose reduction over the 4 year period. The Avutometinib and Defactinib combination may represent a new standard treatment option for platinum-resistant and AI-resistant/recurrent LGSOC who have failed other MEKi.

The greatest benefits of encorafenib plus binimetinib were observed in patients with evidence of high TMB and/or tumor immune infiltration, suggesting potential immune contributions to efficacy, which were not observed with vemurafenib. BRAF V600 detectability in ctDNA appears to have utility as a marker of prognosis and response in this population.

P2, N=63, Active, not recruiting, Pierre Fabre Medicament | Trial completion date: Sep 2026 --> Dec 2026

In recent years, MEK inhibitors like binimetinib and tunlametinib have displayed the efficacy for NRASmut melanoma, with tunlametinib being the first and only approved MEK inhibitor for advanced NRASmut melanoma. Subsequently, we explored current and potential treatment approaches for melanoma, primarily encompassing BRAF inhibitors, MEK inhibitors, and immunotherapy, with a particular focus on their clinical relevance of development. Finally, the challenges in the treatment of melanoma, particularly in immunotherapy and targeted therapy, are summarized and discussed.

CDK4/6 and SHP2 emerge as mediators of intrinsic resistance to BRAF/MEK inhibition in Class 2 & 3 BRAF mutant tumors. Therapeutic strategies combining CDK4/6 or SHP2 inhibitors with BRAF/MEK inhibitors in preclinical models show greater efficacy than BRAF/MEK inhibitors alone in these cancers.

A 69-year-old woman with metastatic colorectal cancer (RAS wild-type, microsatellite instability-high, BRAF V600E mutation) receiving encorafenib/binimetinib plus cetuximab developed Grade 2 IR during her first cetuximab infusion (approximately 98 min after initiation)...After discontinuing the infusion, she was treated with oxygen, d-chlorpheniramine, and famotidine, allowing completion at a reduced rate...The generalizability of the findings is limited due to the single-patient design. Prospective validation comparing H1 alone versus combined H1 + H2 premedication, using predefined infusion-rate algorithms, is warranted.

P1, N=400, Active, not recruiting, Pierre Fabre Medicament | Recruiting --> Active, not recruiting

P1, N=267, Recruiting, Pfizer | N=156 --> 267 | Trial completion date: Sep 2028 --> Apr 2030 | Trial primary completion date: Mar 2027 --> Oct 2028

P2, N=52, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027