molecules of the month

The Hanmi/Genentech type II RAF kinase inhibitor, belvarafenib, is a potent and selective inhibitor of RAF dimers. GNE-9815 was covered last month, which was used to validate the biology supporting clinical trials of belvarafenib. This Nature article shares first-in-human results of belvarafenib in BRAF(V600E) and RAS-mutated solid tumors, with a few responses already observed in the dose escalation phase. In agreement with hypothesis that a type II kinase inhibitor would more effectively inhibit RAF dimers than approved type 1.5 inhibitors, belvarafenib demonstrates activity in patients who progressed on prior type 1.5 BRAF(V600E) kinase inhibitors (e.g. vemurafenib, dabrafenib) and against NRAS-mutant tumors in which prior inhibitors are ineffective. Additionally, in contrast to the type 1.5 inhibitors, no reports of squamous cell carcinoma (SCC) were observed,…