Genentech’s Divarasib Shows Superiority in Head-to-Head Phase III Trial Against Approved KRAS G12C Inhibitors in Non-Small Cell Lung Cancer

• Phase III (Krascendo 1) demonstrates best-in-class potential for patients with previously treated advanced KRAS G12C non-small cell lung cancer
• Divarasib showed clinically meaningful improvements in progression-free survival compared to approved KRAS G12C inhibitors; no new safety signals were observed
• Statistical significance for overall survival was achieved at the interim analysis in this poor-prognosis patient population
• Data will be submitted to health authorities and presented at an upcoming medical meeting

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–$RHHBY–Genentech, a member of the Roche Group (SIX: RO, ROP; OTCQX: RHHBY), announced today positive results from the Phase III Krascendo 1 study evaluating divarasib, an investigational next-generation KRAS G12C inhibitor, against the approved, first generation KRAS G12C inhibitors sotorasib or adagrasib in patients with previously treated KRAS G12C non-small cell lung cancer (NSCLC). The study met its primary and key secondary endpoint, with divarasib achieving clinically meaningful and statistically significant improvements in both progression-free survival (PFS) and overall survival (OS). The safety profile for divarasib remained consistent with previous data, with no new findings detected and the most common treatment-related events being manageable and reversible.

“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, M.D., Ph.D., 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.”

Efficacious treatments for KRAS G12C NSCLC represent a significant unmet need in lung cancer care. The G12C mutation is one of the most common KRAS oncogene mutations, found in approximately 14% of NSCLC cases and associated with poor prognosis for patients.

Genentech is advancing a comprehensive Phase III clinical development program in NSCLC, investigating divarasib as both a monotherapy and as a chemotherapy-free combination, across different disease settings and lines of therapy. The U.S. Food and Drug Administration granted Breakthrough Therapy Designation to divarasib in 2022, and in 2026, Orphan Drug Designation for KRAS G12C non-small cell lung cancer (NSCLC).

Data from the Krascendo 1 study will be presented at an upcoming medical meeting and submitted to health authorities with the aim of bringing this potential treatment option to people with KRAS G12C NSCLC as soon as possible.

About the Krascendo 1 study

The Krascendo 1 study [NCT06497556] is the only global head-to-head study evaluating a Kirsten rat sarcoma virus (KRAS) G12C inhibitor in direct comparison with first generation KRAS G12C inhibitors. This Phase III, randomized, open-label, multicenter study evaluates the efficacy and safety of divarasib monotherapy versus sotorasib or adagrasib in people with previously treated KRAS G12C-mutant advanced or metastatic non-small cell lung cancer. The study includes 338 adults, randomized to receive either divarasib (once daily) or, either sotorasib (once daily) or adagrasib (twice daily). The primary endpoint is blinded independent central review (BICR)-assessed progression-free survival. Secondary endpoint measures include overall survival, confirmed objective response, duration of response, as well as other efficacy and safety measures.

About divarasib

Divarasib is an investigational, next-generation, oral, KRAS G12C inhibitor. It has shown greater potency and selectivity in preclinical studies compared with first generation KRAS G12C-targeting treatments, sotorasib and adagrasib. Divarasib is designed to selectively bind to the KRAS G12C protein, locking the protein in an inactive (“off”) state, thereby turning off its tumor-driving signaling.

Divarasib’s comprehensive clinical development program is anchored by three Phase III studies:

About KRAS G12C non-small cell lung cancer

Despite advances in treatment, lung cancer remains the leading cause of cancer-related deaths worldwide, surpassing the combined mortality rates of breast, prostate, and stomach cancers. Each year, it claims the lives of 1.8 million people, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. KRAS is one of the most frequently mutated genes in lung cancer, occurring in approximately 25% of newly diagnosed lung cancers. The G12C mutation is one of the most common KRAS mutations, found in approximately 14% of NSCLC cases.

The KRAS gene produces the KRAS protein, which acts as a cellular control switch, cycling between an active (“on”) and inactive (“off”) state to regulate cell growth and proliferation, making it a critical target for new therapeutic strategies. The G12C mutation locks the KRAS protein in its active (“on”) state, leading to continuous, unregulated signaling for cell growth, driving tumor proliferation.

About Genentech in Lung Cancer

With a 30-year legacy across oncology, Genentech has been driving innovations in small cell and non-small cell lung cancers that have shaped the treatment paradigm for people living with lung cancer. We are leveraging precision medicine to tackle some of the hardest-to-treat diseases, driven by our passion to deliver functional, real-world care. We are committed to ensuring that innovative solutions reach patients wherever they receive their care, working in lockstep with the community to deliver on our goal to improve outcomes for as many people affected by lung cancer as possible.

About Genentech

Founded 50 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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