Daraxonrasib for Previously Treated RAS-Mutant Non–Small-Cell Lung Cancer
This feels like the first real crack in the "undruggable" non-G12C RAS wall in lung cancer: a pan-RAS(ON) inhibitor with responses across G12D, G12V, and other alleles in patients who had already received platinum and immunotherapy. At the 160–220 mg range (the phase 3 dose is 200 mg), patients who hadn't yet received docetaxel had a 42% response rate, median progression-free survival (PFS) of 8 mos, and median overall survival (OS) of 16 mos, which looks well ahead of what we expect from docetaxel, though that's a cross-trial comparison. The catch is tolerability: about half had grade 3 or higher events, 9 in 10 got rash, and most got diarrhea, so rash prophylaxis and proactive GI management will matter just as it does on PDAC. The randomized RASolve 301 trial against docetaxel is the one to watch before this moves into practice.