Roche’s investigational KRAS G12C inhibitor has beaten Amgen’s Lumakras and Bristol Myers Squibb’s Krazati in a phase 3 trial, furthering its ambitions to establish divarasib as a new standard of care.
The open-label Krascendo 1 trial enrolled 338 people with previously treated, KRAS G12C-mutated non-small cell lung cancer (NSCLC). Patients who had already tried a KRAS G12C inhibitor or pan-KRAS/RAS inhibitor were excluded from the trial. Participants took either divarasib once daily, Lumakras once daily or Krazati twice daily.
Roche linked divarasib to statistically significant improvements in progression-free survival and overall survival, achieving the trial’s primary and key secondary endpoint. The results should establish divarasib as a new standard of care in the patient population, Levi Garraway, M.D., Ph.D., Roche’s chief medical officer, said in a statement. Roche has yet to share any survival numbers from the clinical trial.
The readout validates Roche’s argument that divarasib is a differentiated molecule. Divarasib showed better potency and selectivity than the incumbent KRAS G12C inhibitors during in vitro tests. After cross-trial comparisons suggested the edge translated into better clinical outcomes, Roche axed a study comparing divarasib to the chemotherapy docetaxel and went toe-to-toe with Lumakras and Krazati.
Roche’s successful bet that divarasib would win a head-to-head study could help the KRAS G12C inhibitor come from behind to claim the second-line NSCLC market. The FDA approved Lumakras and Krazati in KRAS G12C-mutated, locally advanced or metastatic NSCLC in 2021 and 2022, respectively. Amgen and BMS have struggled to capitalize on their headstarts over Roche.
Lumakras and Krazati were scientific breakthroughs against a previously undruggable target, but sales have underwhelmed. Analysts tipped Lumakras to generate $347 million in 2022, its first full year on the U.S. market. Lumakras’ sales belatedly passed that target in 2024 and reached $363 million last year. BMS, which acquired Krazati in a $5.8 billion deal, reported $205 million in sales of the drug last year.
Undisclosed details of the divarasib data will shape whether Roche can deliver on its ambition to blast past its rivals’ sales. Roche forecasts (PDF) peak divarasib sales of 1 to 2 billion Swiss francs ($1.2 to $2.5 billion). The company has ongoing trials in first-line advanced or metastatic NSCLC and in an adjuvant lung cancer setting. Metastatic sales account for most of the forecast, Roche said at an event last month.
The company plans to present data at an upcoming medical meeting and submit the results to health authorities. Roche recently listed a filing for approval of divarasib in second-line NSCLC among planned submissions for 2027.