Roche’s next-generation KRAS G12C inhibitor divarasib cut the risk of death by 44 percent compared with the current standard KRAS G12C inhibitors sotorasib or adagrasib in previously treated KRAS G12C-mutated non-small cell lung cancer, in pivotal Phase 3 Krascendo 1 results presented at the ESMO Congress in Madrid on October 25 and published simultaneously in The New England Journal of Medicine. The overall survival hazard ratio was 0.56 (95 percent confidence interval 0.41 to 0.78, p=0.0005), and median overall survival was approximately 18 months on divarasib against 12 months on the control arm.
The design is what gives the result its commercial force. Krascendo 1 did not compare divarasib with chemotherapy or with historical data. It randomised patients against the two drugs that own this market today, Amgen’s sotorasib and Bristol Myers Squibb’s adagrasib, and beat them on survival, the endpoint that matters most for guidelines and pricing. Endpoints News, reporting from Madrid on October 25, framed the presentation the same way, as Roche detailing the magnitude of a win over its direct rivals.
Roche reported no new safety findings. The most common treatment-related adverse events were mainly low grade and manageable, the company said, which matters in a class where tolerability and discontinuations have limited the first-generation drugs.
Divarasib is not yet approved in this setting. Roche chief medical officer Levi Garraway said the company is working closely with health authorities to bring the treatment to patients, and the head-to-head survival data, rather than a response-rate surrogate, is the package it will file on. If regulators accept it, the KRAS G12C market moves from a two-drug first-generation contest to a standard set by the challenger.