Phase I Study of Mosperafenib, a Novel Paradox Breaker B-Raf Proto-Oncogene Serine/Threonine Kinase (BRAF) Inhibitor, in Patients With BRAF V600–Mutant Solid Tumors
Intriguing phase I signal for this next-generation paradox-breaker BRAF inhibitor with brain-penetrant properties. The 24% overall response rate (ORR) as a single agent is striking given that 60% of patients had prior BRAFi exposure, and seeing responses in that pretreated group is the most exciting finding. In BRAF-naïve colorectal cancer (CRC) specifically, a 24% ORR and 7.3-month progression-free survival (PFS) as monotherapy compares favorably to encorafenib/cetuximab in BEACON, which is a bold cross-trial comparison but hard to ignore. Safety looks cleaner than approved BRAFis, with no keratoacanthoma or palmar-plantar erythrodysesthesia, and a lower discontinuation rate. Brain penetrance showed early hints of intracranial benefit worth exploring further. One to watch closely as it moves into combinations.