KRAS G12C inhibitor divarasib outperforms approved drugs
October 28, 2026
The KRAS G12C inhibitor divarasib improved progression-free survival, overall survival and response rates compared with the approved drugs sotorasib and adagrasib in previously treated, KRAS G12C-mutated non-small cell lung cancer (NSCLC). The phase III Krascendo 1 results were presented at the Presidential Symposium of the ESMO Congress 2026.
The trial enrolled 338 patients who had received one to three lines of prior systemic therapy. The control group received sotorasib (91%) or adagrasib (9%).
Median progression-free survival, assessed by blinded independent central review, was 9.8 months versus 5.7 months (hazard ratio 0.58; 95% CI 0.44-0.76; p<0.0001) after a median follow-up of 14.3 months. Median overall survival was 17.7 months versus 12.0 months (hazard ratio 0.56; 95% CI 0.41-0.78; p=0.0005). Confirmed objective response rate improved by 25.8% versus control.
Safety and treatment duration with the KRAS G12C inhibitor divarasib
Grade 3-4 treatment-related adverse events (TRAEs) were less frequent with divarasib, at 24.6% versus 34.5%. Hepatotoxicity was lower, with grade 3-4 alkaline phosphatase increase at 0.6% versus 4.1%, but diarrhoea was higher at 9.0% versus 2.9%. Median treatment duration was 11.3 months versus 5.0 months, and TRAEs leading to discontinuation occurred in 4.8% versus 11.7%.
Why it matters
According to Besse, the approved control drugs have only limited efficacy, and an overall survival benefit against chemotherapy has not been demonstrated. He said the higher potency of divarasib “could translate into a new standard of care.”
Besse also said that sotorasib and adagrasib are still available in only a small number of countries, and that improving drug access is needed for any new RAS-targeting agent to benefit patients.
Median treatment duration more than doubled with divarasib. For payers, that is a cost question in its own right, since it determines how many months of drug spend each patient generates. For background, see our earlier coverage of the economic burden of NSCLC.
Source: ESMO news, Krascendo 1 divarasib results (LBA5), ESMO Congress 2026
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