Roche declares KRAS war on Amgen and Bristol

Head-to-head studies are a risky strategy, but KRAS G12C-mutant lung cancer is now so competitive that it’s a case of going hard or going home. That’s presumably why Roche is taking its contender, divarasib, into a phase 3 second-line trial, Krascendo-1, which will primarily compare progression-free survival against an active control cohort of Amgen’s Lumakras or Bristol Myers Squibb’s Krazati. Both comparator drugs have US accelerated approvals, so Roche is taking the view that by the time it comes to filing divarasib they will have secured full approvals – Krazati’s confirmatory Krystal-12 trial has read out, though Lumakras’s Codebreak-200 led to a complete response letter – and both will be considered standard of care. Roche had earlier revealed plans for Krascendo-1, but it’s only now that the study has appeared on clinicaltrials.gov. Notably, two KRAS G12C fast followers, Merck & Co’s MK-1084 and Lilly’s olomorasib, aren’t even pursuing second-line NSCLC, instead going straight into first-line pivotal trials. Divarasib won’t enter pivotal first-line NSCLC development until next year, but has been studied here in the phase 1/2 Krascendo-170 trial. Beating second-line Lumakras or Krazati on PFS might be a tall order, but Roche might still hope for non-inferiority with better safety.

Phase 3 trials of KRAS G12C inhibitors in lung cancer

Source: OncologyPipeline.