mosperafenib

Mosperafenib (RG6344, RO7276389) is an orally bioavailable, next-generation small-molecule inhibitor of BRAF, specifically designed as a "MAPK paradox breaker." Unlike first-generation BRAF inhibitors (such as vemurafenib or encorafenib), mosperafenib does not induce paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. This paradoxical activation is a common cause of dose-limiting toxicities and secondary malignancies, such as cutaneous squamous cell carcinomas, in patients treated with earlier BRAF inhibitors. Developed by Roche, mosperafenib is intended to provide deeper and more durable target inhibition with an improved safety profile. It is currently being evaluated in Phase 1 clinical trials for the treatment of advanced solid tumors harboring BRAF V600 mutations, including metastatic colorectal cancer, where it is being tested both as a monotherapy and in combination with other agents like cetuximab or cobimetinib.