Genentech's divarasib outperforms approved KRAS G12C inhibitors in Phase III NSCLC trial

Key trial results

The Phase III Krascendo 1 study met its primary and key secondary endpoints: divarasib delivered clinically meaningful and statistically significant improvements in blinded independent central review (BICR)-assessed progression-free survival and achieved statistical significance for overall survival at the interim analysis versus approved KRAS G12C inhibitors sotorasib or adagrasib.

Study design

Krascendo 1 is a global, randomized, open-label, multicenter trial of 338 adults with previously treated KRAS G12C‑mutant advanced or metastatic non‑small cell lung cancer. Patients were randomized to once‑daily divarasib or to either once‑daily sotorasib or twice‑daily adagrasib. Primary endpoint was BICR‑assessed PFS; secondary endpoints included OS, objective response, and duration of response.

Safety

The safety profile for divarasib was consistent with prior data; no new safety signals were identified and the most common treatment‑related events were described as manageable and reversible.

Development and next steps

Divarasib is an investigational, next‑generation oral KRAS G12C inhibitor designed to lock KRAS G12C in an inactive state. Genentech plans to submit the Krascendo 1 data to health authorities and to present the results at an upcoming medical meeting. Divarasib holds FDA Breakthrough Therapy designation (2022) and Orphan Drug designation for KRAS G12C NSCLC (2026).

Disease context

KRAS mutations occur in about 25% of newly diagnosed lung cancers; the G12C mutation is present in roughly 14% of NSCLC and is associated with poor prognosis, representing a significant unmet need.