Key Takeaways:
Roche's experimental KRAS G12C inhibitor divarasib beat Amgen Inc.'s Lumakras and Bristol Myers Squibb Co.'s Krazati in a head-to-head Phase III trial, achieving statistically significant improvements in both progression-free and overall survival in patients with previously treated non-small cell lung cancer.
"These results should establish divarasib as a new standard of care for previously-treated lung cancer patients with this genetically defined tumor subtype," Levi Garraway, chief medical officer at Roche, said in a statement.
The Krascendo 1 study enrolled 338 adults with KRAS G12C-mutant advanced or metastatic NSCLC who had not previously received a KRAS G12C inhibitor. Patients were randomized to receive either divarasib once daily or one of the two approved first-generation inhibitors — sotorasib (Lumakras) once daily or adagrasib (Krazati) twice daily. The trial met its primary endpoint of blinded independent central review-assessed progression-free survival and the key secondary endpoint of overall survival, which achieved statistical significance at the interim analysis. Divarasib's safety profile remained consistent with prior data, with treatment-related adverse events described as manageable and reversible.
The result positions Roche to capture a market that has so far disappointed early entrants. Amgen's Lumakras generated $363 million in sales last year, while BMS's Krazati brought in $205 million — far below the multibillion-dollar forecasts that accompanied their launches as the first drugs to target the once "undruggable" KRAS protein. Roche has forecast peak divarasib sales of 1 billion to 2 billion Swiss francs ($1.2 billion to $2.5 billion), with the metastatic setting accounting for most of that estimate. The KRAS G12C mutation occurs in about 14 percent of NSCLC cases and is associated with poor prognosis.
Competitive landscape
Divarasib is one of several next-generation KRAS G12C inhibitors seeking to displace the first-generation drugs. Merck & Co.'s calderasib and Eli Lilly & Co.'s olomorasib are also in Phase III development, alongside a growing pipeline of KRAS G12D and pan-KRAS candidates. Roche's broader development program includes Krascendo 2, testing divarasib plus Merck's Keytruda (pembrolizumab) as a chemotherapy-free first-line combination, and Krascendo 3, evaluating adjuvant divarasib in early-stage resected NSCLC.
The U.S. Food and Drug Administration granted divarasib Breakthrough Therapy Designation in 2022 and Orphan Drug Designation for KRAS G12C NSCLC in 2026. Roche plans to present the full Krascendo 1 data at an upcoming medical meeting and submit the results to health authorities, with a filing for second-line approval listed among planned submissions for 2027.
For Roche shareholders, the positive readout validates the company's bet that divarasib's greater preclinical potency and selectivity would translate into superior clinical outcomes. The next catalyst is the Krascendo 2 first-line data, which will determine whether divarasib can expand beyond the second-line setting into a larger patient population.
This article is for informational purposes only and does not constitute investment advice.
