Roche’s divarasib demonstrates superiority in head-to-head Phase III trial against approved KRAS G12C inhibitors in non-small cell lung cancer

Roche has announced positive outcomes from the Phase III Krascendo 1 study, which assessed divarasib, an investigational next-generation KRAS G12C inhibitor, head-to-head against the approved first-generation KRAS G12C inhibitors sotorasib or adagrasib in patients with previously treated KRAS G12C non-small cell lung cancer. The trial cleared both its primary and key secondary endpoints, with divarasib delivering clinically meaningful and statistically significant gains across both progression-free survival and overall survival. The safety characteristics of divarasib held firm relative to earlier data, with no new findings identified and the most frequently occurring treatment-related events proving manageable and reversible in nature.

“The superior survival demonstrated in this global head-to-head comparison of KRAS G12C inhibitors confirms the potential of divarasib to improve clinical outcomes for people with KRAS G12C non-small cell lung cancer,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “These results should establish divarasib as a new standard of care for previously-treated lung cancer patients with this genetically defined tumor subtype.”

Effective treatment options for patients with KRAS G12C non-small cell lung cancer remain a pressing unmet need within oncology. The G12C mutation stands among the most prevalent KRAS oncogene mutations, present in approximately 14% of non-small cell lung cancer cases and linked to a poor prognosis.

Roche is progressing an extensive Phase III clinical development programme in non-small cell lung cancer, exploring divarasib both as a standalone therapy and within chemotherapy-free combinations across a range of disease settings and treatment lines. The US Food and Drug Administration awarded divarasib Breakthrough Therapy Designation in 2022, followed by Orphan Drug Designation for KRAS G12C non-small cell lung cancer in 2026.

---

---

Related Topics and Keywords

divarasib, KRAS G12C inhibitors, lung cancer, non-small cell lung cancer, Phase III trial, Roche