Background
Phase 3, open-label, randomized trial; N=829 (413 vs 416). Locally advanced, unresectable, stage III NSCLC without progression after platinum-based concurrent chemoradiation. Tested consolidation anti-TIGIT (tiragolumab) + anti-PD-L1 (atezolizumab) against the PACIFIC standard, durvalumab. Primary analysis population: PD-L1-positive (TC ≥1%; n=419).
Results
Interventions and follow up: Arm A: Tiragolumab 840 mg + atezolizumab 1680 mg IV on day 1 q4w, 13 × 28-day cycles
Arm B: Durvalumab 10 mg/kg q2w or 1500 mg q4w, 13 cycles
Primary endpoint: IRF-assessed PFS in PD-L1+ (TC ≥1%)
mFollow up: 33.0 mo
Results: PFS (PD-L1+): 19.4 vs 16.6 mo; HR 0.96, 95% CI 0.75–1.23, P=.76 — primary endpoint not met
PFS (all-comers): 14.2 vs 13.8 mo; HR 1.00, 95% CI 0.84–1.19
OS (PD-L1+): NE vs 54.8 mo; HR 0.99, 95% CI 0.73–1.34
OS (all-comers): 45.6 vs 45.8 mo; HR 0.98, 95% CI 0.80–1.20
Arm B: Durvalumab 10 mg/kg q2w or 1500 mg q4w, 13 cycles
Primary endpoint: IRF-assessed PFS in PD-L1+ (TC ≥1%)
mFollow up: 33.0 mo
Results: PFS (PD-L1+): 19.4 vs 16.6 mo; HR 0.96, 95% CI 0.75–1.23, P=.76 — primary endpoint not met
PFS (all-comers): 14.2 vs 13.8 mo; HR 1.00, 95% CI 0.84–1.19
OS (PD-L1+): NE vs 54.8 mo; HR 0.99, 95% CI 0.73–1.34
OS (all-comers): 45.6 vs 45.8 mo; HR 0.98, 95% CI 0.80–1.20
Adverse events
Grade ≥3 (any): NR in abstract
Overall: combination tolerated; safety consistent with prior tiragolumab + atezolizumab experience; no new or unexpected signals
Overall: combination tolerated; safety consistent with prior tiragolumab + atezolizumab experience; no new or unexpected signals
Conclusions
Tiragolumab + atezolizumab consolidation was not superior to durvalumab after chemoradiation for unresectable stage III NSCLC — PFS and OS were essentially identical. TIGIT blockade added no benefit in this setting; durvalumab remains the consolidation standard.
Key Limitations
Open-label, superiority design against an active standard — a high bar with no placebo arm. Primary endpoint restricted to the PD-L1+ subset with all-comers secondary. Abstract does not report grade ≥3 AE rates. OS in both arms (~45 mo all-comers) exceeds historical PACIFIC figures, reflecting stage migration and modern staging rather than incremental drug effect.
Clinical Context
Durvalumab consolidation for up to 12 months remains the standard of care after concurrent chemoradiation for unresectable stage III NSCLC (PACIFIC; FDA-approved 2018; NCCN/ESMO). SKYSCRAPER-03 extends the string of anti-TIGIT failures (including SKYSCRAPER-01 in 1L PD-L1-high advanced NSCLC) and effectively closes tiragolumab development in this setting. Osimertinib consolidation (LAURA) applies separately to EGFR-mutant disease.