SKYSCRAPER-02C: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer in China

INTRODUCTION: Tiragolumab may synergize with other immunotherapies to enhance antitumor immune responses. We report efficacy, safety, and biomarker findings from SKYSCRAPER-02C (NCT04665856), comparing tiragolumab plus atezolizumab plus carboplatin/etoposide (CE; experimental arm) with atezolizumab plus CE (control arm) in patients with untreated extensive-stage small-cell lung cancer (ES-SCLC) in China. METHODS: Patients were randomized (1:1) to tiragolumab 600 mg or placebo, plus atezolizumab 1200 mg and CE (four cycles), then maintenance tiragolumab/placebo plus atezolizumab. Primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS) in patients without history/presence of brain metastases at baseline (primary analysis set [PAS]). RESULTS: The PAS comprised 54 patients in the experimental arm and 56 in the control arm. Median PFS was 5.6 months (experimental) and 5.4 months (control; unstratified HR = 0.65, 95% CI: 0.43‒0.97; median follow-up 26.7 months); median OS was 18.7 and 13.5 months, respectively (unstratified HR 0.89, 95% CI: 0.56‒1.40). The biomarker-evaluable population comprised 69 patients with immunohistochemistry data and 66 with RNA sequencing (RNAseq) data. RNAseq survival analysis showed that patients with NMF3 (SCLC-I-NE) or NMF4 (SCLC-I-nNE) molecular subtypes, and those with high T-effector and tumor-associated macrophage immune signatures, benefited from tiragolumab plus atezolizumab plus CE treatment. Tiragolumab was well tolerated with no new safety signals. CONCLUSIONS: While results from the global SKYSCRAPER-02 study were not statistically significant, numerical improvements in PFS and OS were seen with tiragolumab plus atezolizumab plus CE versus atezolizumab plus CE in Chinese patients with ES-SCLC. Biomarker analysis identified immune-inflamed signatures that may guide future TIGIT-based strategies.