The phase 3 Krascendo 1 trial found longer median overall survival with experimental divarasib than with two approved KRAS-targeted drugs for previously treated advanced lung cancer, a setting Genentech says can have limited options.
The study enrolled people with advanced or metastatic non-small cell lung cancer carrying a KRAS G12C mutation. The NEJM paper appeared on Oct. 25, the same day the results were presented at the European Society for Medical Oncology Congress.
The randomized, open-label study assigned 338 participants to treatment: 167 received divarasib and 171 received either sotorasib or adagrasib. Median overall survival was 17.7 months with divarasib and 12.0 months with the comparison drugs. The hazard ratio for death was 0.56 (95% confidence interval, 0.41 to 0.78; p=0.0005), indicating a 44% lower hazard of death in the divarasib group.
Median progression-free survival was 9.8 months with divarasib and 5.7 months with sotorasib or adagrasib. The hazard ratio for disease progression or death was 0.58, indicating a 42% lower hazard. Among 328 patients evaluated for response, the confirmed objective response rate was 58.4% with divarasib and 32.3% with the comparison treatments. Treatment-related grade 3 or 4 adverse events occurred in 24.6% and 34.5% of participants, respectively.
MD Anderson’s summary noted that relatively few participants in the control group received adagrasib and that patients with untreated brain metastases were ineligible. Ferdinandos Skoulidis, a professor of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center and the study’s principal investigator, said “extending survival while delaying cancer progression are the outcomes that matter most.”
Genentech estimates KRAS G12C mutations occur in about 12% to 14% of non-small cell lung cancer cases and says effective options can be limited when the disease returns. The company, a member of the Roche Group, describes divarasib as investigational and is studying it in phase 3 first-line and adjuvant settings. Its Oct. 25 announcement did not provide results dates for those studies.
