Tiragolumab (anti‑TIGIT) + atezolizumab (PD‑L1) + chemo misses PFS/OS vs pembrolizumab‑chemo in 1L nonsquamous NSCLC

SKYSCRAPER‑06 (Phase 3; NCT04619797) randomized previously untreated, locally advanced unresectable/metastatic nonsquamous NSCLC without EGFR/ALK alterations to tiragolumab (anti‑TIGIT) + atezolizumab (anti‑PD‑L1) + pemetrexed/platinum vs placebo + pembrolizumab (anti‑PD‑1) + pemetrexed/platinum (n=542; median follow‑up 11.8 months; enrolled Dec 15, 2020–Sep 14, 2023; data cutoff Apr 19, 2024). Median PFS was 8.3 vs 9.9 months (HR 1.27; 95% CI 1.02–1.57; P=.99) and median OS was 18.9 vs 23.1 months (HR 1.33; 95% CI 1.02–1.73; P=.98), underperforming the pembrolizumab + pemetrexed/platinum benchmark from KEYNOTE‑189 (5‑year update: durable OS/PFS benefit vs chemo; historically median OS ~22 months at final analysis for the pembrolizumab arm). Grade 3–4 AEs were similar (61.4% vs 60.7%), but grade 5 AEs were numerically higher with tiragolumab/atezo (10.1% vs 5.9%); the trial stopped for futility.