Tremelimumab (CTLA-4) + durvalumab (PD-L1) + chemo extends response durability vs pembrolizumab + chemo in STK11/KEAP1/KRASm 1L NSQ mNSCLC

TRITON (Phase 2b, open-label, US; NCT06008093) randomized treatment-naïve, EGFR/ALK WT, non-squamous mNSCLC with STK11, KEAP1 and/or KRAS mutations (n=84; 41 T+D+pemetrexed-platinum vs 43 pembrolizumab+pemetrexed-platinum). At the interim ORR/DoR read (data cutoff Nov 12, 2025; PFS still blinded to sponsor), confirmed ORR was 39.0% vs 34.9% (unconfirmed ORR 48.8% vs 41.9%), and median DoR was NR (95% CI 6.3–NR) vs 6.4 months (4.2–NR) with 100% vs 58.3% still in response at 6 months; in an exploratory KRAS-mut-only subset (n=52), ORR was 48.0% (12/25) vs 33.3% (9/27). Grade 3/4 possibly treatment-related AEs were similar (41.5% vs 41.9%), with low discontinuations (2.4% vs 4.7%) and few treatment-related deaths (0% vs 2.3%); versus the broader, biomarker-unselected KEYNOTE-189 benchmark for pembrolizumab+pemetrexed-platinum (ORR ~48%; mPFS 8.8 months), this IA suggests ORR is not clearly higher in this mutation-enriched population, but response durability may improve with added CTLA-4 blockade.