Bristol joins Lilly with a first-line KRAS triplet

The lung cancer battleground for KRAS G12C inhibitors has moved firmly to the front line, and the latest contender to show its hand here is Bristol Myers Squibb. The just revealed phase 3 study Krystal-4 will test Bristol's Krazati as part of a Keytruda plus chemo triplet in first-line NSCLC patients regardless of PD-L1 expression, a new listing on clinicaltrials.gov shows. Thus Bristol's approach here mirrors that of Lilly, whose Sunray-01 trial tests olomorasib plus Keytruda and chemo in PD-L1 all-comers. A separate part of Sunray-01 gives an olomorasib/Keytruda doublet to patients who express PD-L1 at 50% or above – analogous to the phase 3 portion of Bristol's Krystal-7. The contrast is with the more aggressive stance of Roche, which tests a divarasib/Keytruda doublet against a tougher control of Keytruda plus chemo; meanwhile, Amgen is looking at PD-L1 non-expressers. This shows the still conflicting opinions on how best to make inroads into first-line NSCLC, which ORR data from the phase 2 part of Krystal-7 suggested wouldn't be easy. For its part, Merck & Co's phase 3 effort here with MK-1084 so far involves only a Keytruda combo in the PD-L1 ≥50% setting, while Revolution has yet to show its hand.

Phase 3 studies of KRAS G12C inhibitors in 1st-line NSCLC

Source: OncologyPipeline.