Roche's divarasib outperforms Amgen and Bristol Myers Squibb drugs in Phase 3 lung cancer trial

Roche's experimental drug divarasib outperformed Amgen's Lumakras and Bristol Myers Squibb's Krazati in the Phase 3 Krascendo-1 trial for previously treated KRAS G12C-mutated non-small cell lung cancer. Divarasib demonstrated statistically significant improvements in progression-free and overall survival. While this represents a second-line success, analysts note that the larger commercial opportunity lies in the first-line setting, where Roche is testing divarasib in the Krascendo-2 trial.

Divarasib Phase 3 trial results

• ▪The safety profile of divarasib in the Krascendo-1 trial showed no new safety findings of concern, with most treatment-related side effects being manageable and reversible.
• ▪Roche did not release detailed data from the Krascendo-1 trial, stating that results will be presented at an upcoming medical meeting.
• ▪The Krascendo-1 trial evaluated divarasib as a monotherapy in patients with previously treated KRAS G12C-mutated non-small cell lung cancer.
• ▪Roche's experimental drug divarasib demonstrated statistically significant improvements in progression-free survival and overall survival compared to Amgen's Lumakras and Bristol Myers Squibb's Krazati in the Phase 3 Krascendo-1 trial.

KRAS G12C mutation biology

• ▪The KRAS G12C genetic mutation occurs in approximately 14% of non-small cell lung cancer cases.
• ▪The KRAS G12C mutation locks the KRAS gene's cell growth regulation switch to 'on,' leading to continuous cell growth that drives tumors.

Approved competitor treatments

• ▪Bristol Myers Squibb acquired Krazati's developer, Mirati Therapeutics, for $4.8 billion in 2023.
• ▪In 2025, Lumakras generated $367 million in sales, while Krazati generated $205 million in sales.
• ▪Amgen won the first FDA approval for a KRAS-targeting medicine, Lumakras, in 2021, while Krazati was cleared for sale in 2022.
• ▪Amgen's Lumakras and Bristol Myers Squibb's Krazati were the first KRAS-targeted drugs to reach the market.

Second-line market positioning

• ▪Roche Chief Medical Officer Levi Garraway stated that the Krascendo-1 results should establish divarasib as a new standard of care for previously treated KRAS G12C non-small cell lung cancer patients.
• ▪Lumakras and Krazati sales have been held back by narrow patient populations, drug resistance, reimbursement hurdles, and limited access to KRAS testing.
• ▪Jefferies analyst Michael Leuchten described the Krascendo-1 trial as a small win for Roche but noted it is premature to claim overall victory.

First-line Krascendo-2 trial

• ▪Roche is running the Krascendo-3 trial to evaluate the adjuvant use of divarasib in earlier-stage KRAS G12C-mutant non-small cell lung cancer.
• ▪Roche is testing divarasib in previously untreated patients in the Krascendo-2 trial, which compares divarasib plus Merck & Co.'s Keytruda against Keytruda plus chemotherapy.

Revenue opportunity projections

• ▪Divarasib is one of several second-generation KRAS inhibitors aiming to capture market share, alongside Merck & Co.'s calderasib and Eli Lilly's olomorasib.
• ▪Success in the Krascendo-2 trial could open a revenue opportunity of up to 5 billion Swiss francs, or about $6.2 billion, for Roche.

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