Divarasib Beats Older KRAS Drugs in Lung Cancer Trial
In a phase 3 trial of previously treated KRAS G12C-mutant lung cancer, divarasib cut the risk of death by 44% against sotorasib or adagrasib.
Patients with previously treated, advanced KRAS G12C-mutant non-small cell lung cancer lived longer on the targeted drug divarasib than on the two KRAS inhibitors already approved, researchers at the University of Texas MD Anderson Cancer Center report. The phase 3 Krascendo 1 trial was published in The New England Journal of Medicine and presented at the European Society for Medical Oncology (ESMO) Congress 2026.
The study was led by Ferdinandos Skoulidis, a professor of thoracic and head and neck medical oncology. It enrolled 338 patients at 151 centers in 26 countries. Participants were randomly assigned to divarasib, sotorasib or adagrasib, and all of them had cancer that had progressed after earlier treatment.
Survival and response
Divarasib reduced the risk of disease progression by 42% and the risk of death by 44%. Median overall survival was 17.7 months with divarasib and 12 months with sotorasib or adagrasib.
After a median follow-up of 14.3 months, median progression-free survival was 9.8 months on divarasib against 5.7 months on the standard inhibitors. At one year, 44% of patients on divarasib were free from progression or death, compared with 24% in the control group.
The overall response rate was 58.4% with divarasib and 32.3% with standard therapy. Responses lasted a median of 11.9 months against 6.9 months.
Severe treatment-related side effects occurred in 25% of patients on divarasib and 35% of those on current KRAS-targeted therapies, even though patients received divarasib for twice as long.
About the drug
Divarasib is a next-generation oral therapy that locks the abnormal KRAS protein in an inactive state. About 14% of patients with non-small cell lung cancer carry the KRAS G12C mutation. Sotorasib and adagrasib were the first approved drugs designed to target it.
"Divarasib significantly improved both measures compared with currently available KRAS inhibitors," Skoulidis said. "These results establish divarasib as a new standard of care and offer hope for patients whose treatment options have been limited after their cancer progresses."
Krascendo 1 is the first phase 3 trial to compare a next-generation KRAS inhibitor directly with approved KRAS-targeted treatments. The researchers note that the trial was open-label, that few patients in the control group received adagrasib, and that patients with untreated brain metastases were not eligible.
Source: News-Medical