Basel, Switzerland, July 2, 2026
Roche has announced positive top-line results from its pivotal Phase III Krascendo 1 clinical trial, demonstrating that its investigational next-generation KRAS G12C inhibitor, divarasib, significantly outperformed currently approved first-generation KRAS G12C inhibitors in patients with previously treated advanced or metastatic non-small cell lung cancer (NSCLC). The global head-to-head study achieved both its primary endpoint of progression-free survival (PFS) and its key secondary endpoint of overall survival (OS), highlighting divarasib’s potential to become a new standard of care for patients with KRAS G12C-mutated NSCLC. Importantly, the investigational therapy demonstrated clinically meaningful and statistically significant improvements over sotorasib and adagrasib, while maintaining a consistent and manageable safety profile with no new safety concerns identified. Roche confirmed that the findings will be submitted to regulatory authorities worldwide and presented at an upcoming international medical conference as the company advances the therapy toward regulatory approval.
Phase III Trial Demonstrates Superior Survival Outcomes
The Krascendo 1 study is the first global Phase III head-to-head clinical trial directly comparing one KRAS G12C inhibitor against currently approved therapies in patients with previously treated KRAS G12C-mutant NSCLC. The randomized, multicenter, open-label trial enrolled 338 adult patients, who received either once-daily divarasib or one of the approved KRAS G12C inhibitors, sotorasib or adagrasib. According to Roche, divarasib delivered statistically significant improvements in progression-free survival, while also achieving overall survival significance during the interim analysis, an especially meaningful outcome for a patient population facing poor prognoses and limited treatment options.
Researchers reported that the therapy’s adverse events remained largely manageable, reversible, and consistent with previous clinical studies, reinforcing its favorable benefit-risk profile. Roche believes these data further strengthen the scientific rationale for positioning divarasib as a best-in-class targeted therapy for genetically defined lung cancer patients carrying the KRAS G12C mutation.
Next-Generation KRAS Inhibitor Targets Critical Unmet Need
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The KRAS G12C mutation represents one of the most common oncogenic drivers in lung cancer, occurring in approximately 14% of non-small cell lung cancer cases, and is associated with aggressive disease progression and poor clinical outcomes. Unlike first-generation inhibitors, divarasib has been specifically engineered to provide greater potency and selectivity, binding the mutated KRAS G12C protein and locking it into its inactive state to halt tumor-driving signaling pathways. Roche continues to expand the clinical development program through three major Phase III studies, evaluating divarasib as both monotherapy and chemotherapy-free combination therapy across early-stage, first-line, and previously treated NSCLC settings.
The investigational medicine has already received FDA Breakthrough Therapy Designation and Orphan Drug Designation for KRAS G12C-mutant NSCLC, reflecting its potential to address a significant unmet medical need for patients with genetically driven lung cancer.
Roche Expands Precision Oncology Leadership
The success of the Krascendo 1 trial further strengthens Roche’s leadership in precision oncology, where therapies are developed based on specific genetic alterations rather than tumor location alone. Roche has built a comprehensive oncology portfolio that combines targeted therapies, immunotherapies, companion diagnostics, and genomic testing to personalize treatment decisions and improve patient outcomes. In addition to approved medicines including Alecensa®, Tecentriq®, and Rozlytrek®, the company continues investing heavily in next-generation targeted medicines designed to address actionable genomic alterations across lung cancer and other malignancies.
With regulatory submissions now planned following these positive Phase III findings, divarasib could soon become a major advancement in precision treatment for KRAS G12C-positive NSCLC, potentially offering improved survival outcomes for thousands of patients worldwide while reinforcing the growing role of genomics-driven cancer therapeutics in modern oncology.
Source: Roche press release
