P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

Outcomes following progression on chemotherapy and MAPK-targeted therapy with Encorafenib plus Cetuximab remain poor, highlighting an unmet need for effective later-line treatments. We discuss the mechanistic framework by which a subset of BRAFV600E-mutant MSS mCRC may respond to immune checkpoint inhibition through an inflamed immune microenvironment driven by constitutive MAPK signalling. This case illustrates the interplay between tumour-agnostic biomarkers such as TMB-high and tumour-specific context, and highlights the value of longitudinal genomic profiling, including ctDNA, to identify resistance mechanisms and guide treatment selection.

P1, N=159, Recruiting, Haisco Pharmaceutical Group Co., Ltd.

P2, N=25, Recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Active, not recruiting --> Recruiting

P2, N=25, Not yet recruiting, Vall d'Hebron Institute of Oncology

P2, N=254, Recruiting, Fore Biotherapeutics | N=134 --> 254

P4, N=46, Recruiting, Pfizer | N=71 --> 46

Vemurafenib and dabrafenib are two selective BRAF inhibitors approved by the FDA for clinical use. Molecular dynamics and metadynamics simulations were performed in the Desmond module of the academic version of the Schrödinger-Maestro 2021-4 program, utilizing the OPLS-2005 force field. Finally, all the protein figures presented in this article were made in the PyMOL program and the RMSD graphics were made in the statistical package R and RStudio 2025.05.1.

P2, N=15, Completed, Scripps Health | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Apr 2026 | Trial primary completion date: Dec 2026 --> Apr 2026

Vemurafenib increases miR-31-5p in keratinocyte-derived exosomes, which suppresses ALKBH1 and elevates RNA m6A in melanoma cells, thereby promoting proliferation and reducing vemurafenib sensitivity. Targeting the miR-31-5p/ALKBH1 axis and m6A modification may offer a potential therapeutic strategy to enhance vemurafenib sensitivity in BRAFV600E melanoma cells.

P1, N=47, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | N=33 --> 47

This study investigates the synergistic effects of capivasertib, an Akt pathway inhibitor, in combination with B-Raf inhibitors (vemurafenib and encorafenib) in B-Raf-mutated melanoma models. Systemic toxicity analyses revealed no significant changes in body weight or serum markers of pancreatic, kidney, or liver function. These findings establish capivasertib and B-Raf inhibitor combinations as a safe and effective strategy for overcoming resistance B-Raf-mutated melanoma, providing new insights into the potential of dual pathway targeting.