SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1–High, Locally Advanced, Unresectable or Metastatic Non–Small Cell Lung Cancer

Abstract

PURPOSE Tiragolumab plus atezolizumab has shown encouraging survival outcomes in metastatic non–small cell lung cancer (NSCLC), primarily in patients with PD-L1–high tumors. We further evaluated the combination of tiragolumab plus atezolizumab in the phase III SKYSCRAPER-01 study. METHODS Patients with untreated, locally advanced unresectable/metastatic PD-L1–high (by central laboratory testing) NSCLC were randomly assigned 1:1 to receive either tiragolumab (600 mg) plus atezolizumab (1,200 mg) or placebo plus atezolizumab (1,200 mg) intravenously in 21-day cycles until disease progression, loss of clinical benefit, or unacceptable toxicity. Primary end points were investigator-assessed progression-free survival (INV-PFS) and overall survival (OS) in the primary analysis set (PD-L1–high per 22C3 assay). RESULTS Five hundred twenty-one patients were randomly assigned to either the tiragolumab plus atezolizumab group (n = 262) or the placebo plus atezolizumab group (n = 259). At the primary PFS analysis (Mar 12, 2022; median follow-up 9.9 months [IQR, 6.2-13.8]), median INV-PFS was 7.0 months (95% CI, 5.6 to 9.8) with tiragolumab plus atezolizumab and 5.6 months (95% CI, 4.4 to 7.0) with placebo plus atezolizumab (hazard ratio [HR], 0.78 [95% CI, 0.63 to 0.97]; P = .02 [nonsignificant]). At the final OS analysis (Sept 24, 2024; median follow-up 17.9 months [IQR, 6.7-39.0]), median OS was 23.1 months (95% CI, 17.7 to 28.8) with tiragolumab plus atezolizumab and 16.9 months (95% CI, 14.6 to 21.3) with placebo plus atezolizumab (HR, 0.87 [95% CI, 0.7 to 1.1]; P = .22 [nonsignificant]). Overall, 41.2% (n = 110/267) and 33.8% (n = 89/263) of patients experienced grade 3-4 adverse events with tiragolumab plus atezolizumab and placebo plus atezolizumab, respectively. Four and two treatment-related deaths occurred in each group, respectively. CONCLUSION Tiragolumab plus atezolizumab did not demonstrate a statistically significant INV-PFS or OS benefit over atezolizumab in patients with previously untreated PD-L1–high NSCLC.