Roche: Divarasib outperforms first‑generation KRAS G12C inhibitors in phase III Krascendo 1
- Krascendo 1 randomised 338 adults with previously treated KRAS G12C advanced or metastatic NSCLC.
- Divarasib achieved clinically meaningful, statistically significant improvements in progression‑free survival versus sotorasib or adagrasib.
- Overall survival reached statistical significance at interim analysis in this poor‑prognosis population.
- Safety profile consistent with prior data; no new safety signals and most treatment‑related events were manageable and reversible.
Key results
The phase III Krascendo 1 study met its primary and key secondary endpoints: divarasib produced clinically meaningful and statistically significant improvements in blinded independent central review‑assessed progression‑free survival and in overall survival versus the approved first‑generation KRAS G12C inhibitors sotorasib or adagrasib. Statistical significance for overall survival was achieved at the interim analysis. The safety profile remained consistent with prior data, with no new findings and the most common treatment‑related events described as manageable and reversible.
Study design
Krascendo 1 is a randomised, open‑label, global phase III trial enrolling 338 adults with previously treated KRAS G12C‑mutant advanced or metastatic non‑small cell lung cancer. Participants were randomised to divarasib (once daily) or to sotorasib (once daily) or adagrasib (twice daily). The primary endpoint was BICR‑assessed progression‑free survival; secondary endpoints included overall survival, confirmed objective response and duration of response.
Divarasib development and regulatory status
Divarasib is an investigational next‑generation oral KRAS G12C inhibitor that showed greater potency and selectivity versus sotorasib and adagrasib in preclinical studies. The US FDA granted Breakthrough Therapy Designation in 2022 and Orphan Drug Designation for KRAS G12C NSCLC in 2026. Roche is running a development programme including Krascendo 2 (first‑line chemo‑free combination with pembrolizumab versus chemotherapy plus pembrolizumab) and Krascendo 3 (adjuvant divarasib versus immunotherapy or observation).
Next steps and context
Data from Krascendo 1 will be presented at an upcoming medical meeting and submitted to health authorities with the stated aim of regulatory review and potential availability for patients with KRAS G12C NSCLC. The G12C mutation occurs in roughly 14% of NSCLC cases and is associated with poor prognosis, underpinning the clinical need addressed by these trials.
Source: Roche
