By VETTAPHARMA reporter – Derek Roche: Roche’s divarasib demonstrated superior progression-free survival and overall survival compared with the approved KRAS G12C inhibitors sotorasib and adagrasib in the pivotal Phase 3 Krascendo 1 trial involving patients with previously treated KRAS G12C-mutant non-small cell lung cancer.
The positive head-to-head results position divarasib as a potential new standard of care and support planned regulatory submissions to health authorities.
The Krascendo 1 (NCT06497556) study is the first global, randomized, open-label, multicenter Phase 3 trial to directly compare a next-generation KRAS G12C inhibitor with first-generation KRAS G12C inhibitors. The study enrolled 338 adults with previously treated advanced or metastatic KRAS G12C-mutant non-small cell lung cancer, who were randomized to receive divarasib once daily or physician-selected sotorasib once daily or adagrasib twice daily. The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival, with key secondary endpoints including overall survival, objective response, duration of response, and safety.
The trial met both its primary endpoint and key secondary endpoint, with divarasib demonstrating clinically meaningful and statistically significant improvements in both progression-free survival and overall survival compared with the approved KRAS G12C inhibitors. Statistical significance for overall survival was achieved at the interim analysis. Roche reported that the safety profile remained consistent with previous studies, with no new safety signals identified and treatment-related adverse events described as manageable and reversible.
KRAS G12C is one of the most common KRAS mutations in non-small cell lung cancer, occurring in approximately 14% of cases and is associated with poor prognosis. Roche noted that divarasib has previously received Breakthrough Therapy Designation from the U.S. FDA and was granted Orphan Drug Designation in 2026 for KRAS G12C-mutant non-small cell lung cancer. The company plans to present the Phase 3 data at an upcoming medical meeting and submit the results to regulatory authorities.
Quick FAQs
1. What Is Divarasib?
Divarasib is an investigational, next-generation, oral KRAS G12C inhibitor designed to selectively bind the KRAS G12C protein and block tumour-driving signalling in cancer cells.
2. What Happened?
Roche announced that divarasib met the primary and key secondary endpoints in the Phase 3 Krascendo 1 study, demonstrating superior progression-free survival and overall survival compared with sotorasib and adagrasib in previously treated KRAS G12C-mutant non-small cell lung cancer.
3. What Is The Krascendo 1 Study?
Krascendo 1 (NCT06497556) is a global, randomized, open-label, multicenter Phase 3 trial involving 338 adults with previously treated advanced or metastatic KRAS G12C-mutant non-small cell lung cancer. It compares divarasib with sotorasib or adagrasib, with progression-free survival as the primary endpoint.
4. What Is KRAS G12C-Mutant Non-Small Cell Lung Cancer?
KRAS G12C-mutant non-small cell lung cancer is a genetically defined subtype of lung cancer caused by a mutation that locks the KRAS protein in an active state, driving continuous tumour growth. The mutation occurs in approximately 14% of non-small cell lung cancer cases.
5. What Were The Key Results?
Divarasib significantly improved both progression-free survival and overall survival versus approved first-generation KRAS G12C inhibitors. No new safety signals were observed, and treatment-related adverse events were manageable and reversible.
6. Why Is This Important?
The head-to-head Phase 3 results suggest that divarasib could become a new standard of care for previously treated KRAS G12C-mutant non-small cell lung cancer and support upcoming regulatory submissions worldwide.
