Serplulimab versus placebo plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: Efficacy and safety from the end-of-study analysis of the international phase 3 ASTRUM-005 study.

8093 Background: ASTRUM-005 is a randomized, double-blind, phase 3 trial comparing the efficacy and safety of anti-PD-1 antibody serplulimab plus chemotherapy (chemo) versus (vs) placebo plus chemo as first-line therapy for extensive-stage small-cell lung cancer (ES-SCLC). Significantly prolonged overall survival (OS) in the serplulimab arm was observed at interim analysis and sustained OS improvement at extended follow-up (2024 ASCO Annual Meeting No. 8100). Here we present end-of-study analysis of ASTRUM-005 at a median follow-up of 42.4 months. Methods: Patients with ES-SCLC who had not received prior systemic therapy were randomized 2:1 to receive serplulimab plus chemo (carboplatin and etoposide) or placebo plus chemo. Serpluliamb or placebo were administered intravenously at 4.5 mg/kg every 3 weeks. Up to 4 cycles of intravenous carboplatin and etoposide were given every 3 weeks. Stratification factors included PD-L1 expression level, brain metastases, and age. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response rate, duration of response, and safety. Results: Between Sep 12, 2019 and Apr 27, 2021, 585 patients were randomized (serplulimab group, n = 389; placebo group, n = 196) and received at least one dose of study treatment. All 585 patients were included in efficacy and safety analyses. As of data cutoff on May 7, 2024, consistent with previous reports, marked improvement in OS, PFS, ORR, and DOR were achieved by patients receiving serplulimab plus chemo than those receiving placebo plus chemo. Median OS was 15.8 vs.11.1 months (stratified HR 0.60, 95% CI 0.49–0.73) for respective arms; estimated 4-year OS rate (95% CI) was 21.9% (17.6–26.6) and 7.2% (3.8–12.1). Subgroup analysis of OS by age, sex, race, ethnicity, ECOG PS, smoking history, brain metastasis, or PD-L1 expression level revealed similar trends of improvement in the serplulimab arm. Median PFS according to independent radiology review committee (IRRC) assessment per RECIST v1.1 was 5.8 vs 4.3 months (stratified HR 0.47, 95% CI 0.38–0.57), respectively. The safety profile was consistent with previous findings. Serplulimab/placebo-related treatment-emergent adverse events of grade 3 or higher occurred in 136 (35.0%) and 57 (29.1%) patients in respective arms. No new safety signals were identified in this study. Conclusions: This end-of-study analysis showed that addition of serplulimab to chemo continued to confer survival benefit to previously untreated patients with ES-SCLC along with manageable safety. These results support serplulimab plus chemo for first-line treatment of ES-SCLC. Clinical trial information: NCT04063163 .