SKYSCRAPER-03: A Phase III Study of Tiragolumab Plus Atezolizumab Versus Durvalumab in Locally Advanced, Unresectable, Stage III NSCLC After Platinum-Based Concurrent Chemoradiation.

BACKGROUND: SKYSCRAPER-03 (NCT04513925) was a phase III, open-label, randomized, study that evaluated consolidation therapy with tiragolumab plus atezolizumab versus durvalumab in patients with locally advanced, unresectable, stage III, non-small cell lung cancer (NSCLC) after platinum-based concurrent chemoradiation. PATIENTS AND METHODS: Eligible patients were randomized (1:1) to receive either atezolizumab (1680 mg every 4 weeks [Q4W]) plus tiragolumab (840 mg Q4W) on day 1 of each cycle, or durvalumab (10 mg/kg every 2 weeks or 1500 mg Q4W for those ≥30 kg body weight) on days 1 and 15 of each cycle, for 13 x 28-day cycles. The primary endpoint was Independent Review Facility (IRF)-assessed progression-free survival (PFS) in patients with programmed cell death ligand-1-positive (PD-L1+; tumor cells [TC] ≥1%) NSCLC. Key secondary endpoints were overall survival (OS) and safety. RESULTS: The PD-L1 all-comers population included 413 patients randomly assigned to tiragolumab plus atezolizumab and 416 to durvalumab; the PD-L1+ population included 209 and 210 patients in each arm, respectively. After a median follow-up of 33.0 months, median IRF-assessed PFS in PD-L1+ patients was 19.4 months with tiragolumab plus atezolizumab versus 16.6 months with durvalumab (stratified hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.75-1.23; p = 0.76); median PFS in PD-L1 all-comers was 14.2 versus 13.8 months, respectively (stratified HR 1.00; 95% CI, 0.84-1.19). Median OS in PD-L1+ patients was not estimable with tiragolumab plus atezolizumab versus 54.8 months with durvalumab (stratified HR 0.99; 95% CI 0.73-1.34); in PD-L1 all-comers, median OS was 45.6 versus 45.8 months, respectively (stratified HR 0.98; 95% CI 0.80-1.20). The safety profile of the combination was consistent with prior observations, and there were no new or unexpected findings. CONCLUSIONS: The primary endpoint of the SKYSCRAPER-03 study was not met. Tiragolumab plus atezolizumab was tolerated but did not offer additional benefit over durvalumab.