Chemotherapy-Free Combination Shows Early Promise for KRAS G12C-Mutant Lung Cancer

KRAS G12C is one of the most common single targetable mutations in non-small cell lung cancer (NSCLC), but until recently most first-line treatment for KRAS-mutant disease still relied on immunotherapy combined with chemotherapy. A phase 1b/2 study is now testing whether a chemotherapy-free approach can work instead.

The KRAScendo-170 study is evaluating divarasib, a next-generation KRAS G12C inhibitor, in combination with pembrolizumab, a standard PD-1 checkpoint immunotherapy, as an initial treatment for newly diagnosed advanced NSCLC patients carrying the KRAS G12C mutation. Early results reported a response rate of roughly 70% in the combination arm, with a median progression-free survival of 19.3 months among patients whose tumors also expressed PD-L1.

Researchers described the results as encouraging enough to support a global phase 3 trial, which is now enrolling patients. If later-stage results confirm the early signal, a chemotherapy-free combination could offer a meaningfully different side-effect profile for eligible patients compared with today's chemotherapy-containing standard regimens.

KRAS was long considered an "undruggable" target in cancer research before the development of G12C-specific inhibitors earlier this decade. See how KRAS-directed and other targeted-therapy trials compare in volume on our live Research Progress Tracker.