Phase 3 calderasib (MK-1084) KRAS G12C inhibitor + durvalumab PD-L1 antibody after CCRT

Merck Sharp & Dohme (Merck/MSD) is running KANDLELIT-015 (MK-1084-015), a Phase 3 randomized, triple-blind, parallel-group trial in unresected stage II (node-positive) to stage III, predominantly nonsquamous NSCLC with confirmed KRAS G12C and known PD-L1 status after definitive platinum-based concurrent chemoradiotherapy without progression. Participants receive oral calderasib (MK-1084), a selective small-molecule KRAS G12C inhibitor, plus AstraZeneca’s durvalumab, a PD-L1 (CD274)–blocking monoclonal antibody, versus placebo plus durvalumab. The primary goal is to test whether adding KRAS G12C inhibition can extend progression-free survival beyond durvalumab consolidation alone, while also characterizing safety and tolerability in the post-CCRT setting. Commercially, this is a biomarker-selected attempt to improve on the PACIFIC-era approach where today’s care for unresectable stage III NSCLC is concurrent chemoradiation followed by durvalumab consolidation; targeted KRAS G12C drugs are otherwise mainly used in advanced/metastatic disease rather than as consolidation after curative-intent therapy.