Tiragolumab combined with atezolizumab has previously shown promising survival outcomes in patients with metastatic non–small cell lung cancer (NSCLC), particularly in those with high programmed death-ligand 1 (PD-L1) expression. SKYSCRAPER-01 (NCT04294810) is a phase 3, double-blind, placebo-controlled, randomized trial designed to evaluate the efficacy and safety of first-line tiragolumab and atezolizumab in patients with PD-L1–high NSCLC.

Eligible patients included those with previously untreated, locally advanced unresectable or metastatic NSCLC with high PD-L1 expression (tumor proportion score [TPS] ≥50%), and EGFR/ALK wildtype status. Participants were randomized 1:1 to receive either tiragolumab 600 mg intravenously (IV) plus atezolizumab 1200 mg IV or placebo plus atezolizumab 1200 mg IV every 3 weeks until disease progression, unacceptable toxicity, or loss of clinical benefit. The primary endpoints were investigator-assessed progression-free survival (INV-PFS) and overall survival (OS) in the primary analysis set (TPS ≥50%; 22C3 assay). Secondary endpoints included investigator assessed (INV)-objective response rate (INV-ORR) and INV-duration of response (INV-DOR) in the primary analysis set, as well as OS in the secondary analysis set (SAS; tumor cell ≥50%; SP263 assay).

A total of 534 patients were randomized, with 266 receiving tiragolumab and 268 receiving placebo. Patient characteristics were well balanced between treatment arms. At the final PFS analysis, after a median follow-up of 9.9 months, the median INV-PFS was 7.0 months in the tiragolumab arm compared with 5.6 months in the placebo (hazard ratio [HR], 0.78; 95% CI, 0.63-0.97; P=.02). At the final OS analysis, after a median follow-up of 17.9 months, the median OS was 23.1 months with tiragolumab versus 16.9 months with placebo (HR, 0.87; 95% CI, 0.71-1.08; P=.22). The tiragolumab combination demonstrated an acceptable safety profile that was consistent with prior observations.

Although the SKYSCRAPER-01 study did not meet its primary endpoints of INV-PFS and OS, numerical improvements in both endpoints with tiragolumab in combination with atezolizumab suggest potential antitumor activity of TIGIT targeting in NSCLC. These findings indicate that further investigation may be warranted.

Source:

Peters S, et al. SKYSCRAPER-01: A phase III, randomized trial of tiragolumab (tira) + atezolizumab (atezo) versus placebo (pbo) + atezo in patients (pts) with previously-untreated PD-L1-high, locally advanced unresectable/metastatic NSCLC. Presented at: American Association for Cancer Research. April 28, 2025; Chicago, IL. Abstract CT051.