A protocol pre-specified interim overall survival analysis of the randomised phase III GEMSTONE-302 trial: sugemalimab or placebo plus platinum-based chemotherapy for first-line metastatic non-small-cell lung cancer

Abstract In the primary analysis of the GEMSTONE-302 trial, sugemalimab plus platinum-based chemotherapy conferred significantly longer progression-free survival (PFS) versus placebo in patients with previously untreated metastatic non-small-cell lung cancer (NSCLC) with no known driver oncogene alterations. Here we report data from a protocol pre-specified interim overall survival (OS) analysis of that trial. In this randomised, double-blind, phase III trial (NCT03789604), adult patients with systemic-treatment-naïve stage IV NSCLC and no known driver oncogene alterations were randomised 2:1 to receive sugemalimab (1200 mg, intravenously) or placebo plus platinum-based chemotherapy every 3 weeks for up to four cycles, followed by maintenance therapy with intravenous sugemalimab or placebo plus pemetrexed (non-squamous NSCLC) or sugemalimab or placebo (squamous NSCLC). Placebo-treated patients could cross over to receive sugemalimab monotherapy upon disease progression. As of 22 November 2021 [median follow-up, 25.4 months (sugemalimab) vs 24.9 months (placebo)], median OS was 25.4 months [95% confidence interval (CI) 20.1-not reached] and 16.9 months (95% CI 12.8–20.7) for the sugemalimab and placebo groups, respectively [hazard ratio (HR) 0.65, 95% CI 0.50–0.84; P = 0.0008]. Median investigator-assessed PFS was 9.0 months (95% CI 7.4–10.9) and 4.9 months (95% CI 4.8–5.2), respectively (HR 0.49, 95% CI 0.40–0.61; P < 0.0001). The OS and PFS benefit with sugemalimab was maintained regardless of histology types and programmed death-ligand 1 (PD-L1) expression. Sugemalimab-treated patients had a significantly higher objective response rate (ORR) versus placebo (63.4% versus 40.3%; P < 0.0001) with a longer median duration of response [9.9 months (95% CI 8.6–13.2) versus 4.4 months (95% CI 3.5–6.1)]. There were no new safety signals. Sugemalimab plus chemotherapy conferred a statistically significant and clinically meaningful improvement in OS and PFS regardless of PD-L1 expression and histology types, supporting sugemalimab as a new first-line treatment option for metastatic NSCLC.