Multicenter phase 3 trial of atezolizumab plus chemotherapy with or without tiragolumab for untreated extensive-stage small cell lung cancer

The TIGIT-targeted monoclonal antibody tiragolumab may synergize with other immunotherapies to enhance antitumor immune responses. The multicenter phase 3 SKYSCRAPER-02C study in China evaluated atezolizumab plus carboplatin-etoposide (CE) chemotherapy with tiragolumab (experimental arm; n=54) or with placebo (control arm; n=56) in patients with previously untreated extensive-stage small cell lung cancer (ES-SCLC). The median progression-free survival was 5.6 months in the experimental arm versus 5.4 months in the control arm (unstratified HR 0.65; 95% CI 0.43-0.97; median follow-up 26.7 months); median overall survival was 18.7 and 13.5 months, respectively (0.89; 0.56-1.40). The biomarker-evaluable population comprised 69 patients with immunohistochemistry data and 66 with RNA sequencing data. Patients with NMF3 or NMF4 molecular subtypes, and those with hig T-effector and tumor-associated macrophage immune signatures, benefited from addition of tiragolumab to atezolizumab-CE. Tiragolumab was well tolerated with no new safety signals. The authors conclude that numerical improvements in survival outcomes were seen with addition of tiragolumab, and that biomarker analysis identified signatures that may guide tiragolumab-based strategies (graphical abstract).