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 SCLC 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 and etoposide (CE; experimental arm) with atezolizumab plus CE (control arm) in patients with untreated extensive-stage SCLC (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 or placebo plus atezolizumab. Primary end points were investigator-assessed progression-free survival (PFS) and overall survival (OS) in patients without history or presence of brain metastases at baseline (primary analysis set).

RESULTS

The primary analysis set 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 hazard ratio = 0.65, 95% confidence interval: 0.43‒0.97; median follow-up 26.7 months); median OS was 18.7 and 13.5 months, respectively (unstratified hazard ratio 0.89, 95% confidence interval: 0.56‒1.40). The biomarker-evaluable population comprised 69 patients with immunohistochemistry data and 66 with RNA sequencing data. RNA sequencing survival analysis found that patients with non-negative matrix factorization 3 (SCLC-inflamed-neuroendocrine) or non-negative matrix factorization 4 (SCLC-inflamed-non-neuroendocrine) 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

Although results from the global SKYSCRAPER-02 study were not statistically significant, numerical improvements in PFS and OS were observed 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 tyrosine-based inhibitory motif domain-based strategies.