Roche has announced positive topline results from its Phase 3 Krascendo 1 study, demonstrating that its investigational next-generation KRAS G12C inhibitor, divarasib, significantly outperformed the currently approved first-generation KRAS G12C inhibitors, sotorasib and adagrasib, in patients with previously treated KRAS G12C-mutated Non-Small Cell Lung Cancer (NSCLC).

The global head-to-head study met both its primary endpoint of progression-free survival (PFS) and key secondary endpoint of Overall Survival (OS), with divarasib delivering clinically meaningful and statistically significant improvements over the existing therapies. Roche also reported that divarasib's safety profile remained consistent with previous clinical findings, with no new safety concerns identified. The most common treatment-related adverse events were manageable and reversible.

Commenting on the findings, Levi Garraway, Chief Medical Officer and Head of Global Product Development, Roche, said the superior survival benefit demonstrated in the study reinforces divarasib’s potential to improve outcomes for patients with KRAS G12C NSCLC. He added that the results position the investigational therapy to become a potential new standard of care for previously treated patients with this genetically defined form of lung cancer.

KRAS G12C is one of the most common KRAS oncogene mutations, occurring in approximately 14 percent of NSCLC cases, and is associated with poor patient prognosis. Despite recent advances, effective treatment options remain limited, highlighting a significant unmet need in this patient population.

Roche is currently advancing a broad Phase 3 clinical development programme for divarasib across multiple NSCLC settings. The programme includes evaluating the therapy as a standalone treatment as well as in chemotherapy-free combination regimens across different lines of therapy.

The investigational therapy has already received Breakthrough Therapy Designation from the US Food and Drug Administration (FDA) in 2022, followed by Orphan Drug Designation in 2026 for KRAS G12C NSCLC.

Roche plans to present detailed findings from the Krascendo 1 study at an upcoming medical conference and submit the data to regulatory authorities to support marketing approvals.

Divarasib is an oral, next-generation KRAS G12C inhibitor designed to selectively bind to the KRAS G12C protein and lock it into an inactive state, thereby blocking tumour-driving signalling. Preclinical studies have demonstrated greater potency and selectivity compared with first-generation KRAS G12C inhibitors.