LBA9 - Updated results of first-line serplulimab versus placebo combined with chemotherapy in extensive-stage small cell lung cancer: An international multicentre phase III study (ASTRUM-005)

Background

PD-L1 inhibitors have been approved for the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC) in combination with chemotherapy (chemo), marking a milestone in the management of this disease. Whether a PD-1 inhibitor provides similar or better benefits in the same patient population remains unclear. At 2022 ASCO Annual Meeting, we presented the results from the interim analysis of a phase 3 study of serplulimab, a novel anti-PD-1 antibody, in combination with chemo in previously untreated ES-SCLC patients. Here we report the updated results after another 7.5 months of follow-up, and the efficacy in subgroups.

Methods

In this randomised, double-blind, international, multicentre, phase 3 study (NCT04063163), patients with ES-SCLC who had not received prior systemic therapy were randomised 2:1 to receive serplulimab 4.5 mg/kg or placebo combined with carboplatin and etoposide intravenously every 3 weeks. The primary endpoint was OS. Secondary endpoints included PFS, ORR, DOR, and safety.

Results

Between Sept 12, 2019 and Apr 27, 2021, 585 patients were randomised (serplulimab group, n = 389; placebo group, n = 196). As of data cutoff (June 13, 2022), median follow-up duration was 19.7 months. Median OS was significantly improved in serplulimab group than that in placebo group (15.8 vs. 11.1 months; HR 0.62, 95% CI 0.50–0.76; P <0.001). Median PFS assessed by IRRC per RECIST v1.1 was also prolonged with the addition of serplulimab (5.8 vs. 4.3 months; HR 0.47, 95% CI 0.38–0.58). Subgroup analysis of OS by race showed similar trends to improved survival in Asians (HR 0.65, 95% CI 0.51–0.84) and non-Asians (HR 0.51, 95% CI 0.33–0.79). Grade ≥3 treatment-related adverse events (AEs) were reported in 75.6% and 75.5% patients in the respective groups. Five patients died from AEs related to serplulimab and one from AE related to placebo.

Conclusions

The promising efficacy and favourable safety of serplulimab plus chemo for untreated ES-SCLC were maintained. Subgroup analysis revealed consistent survival benefits. ASTRUM-005 supports the development of serplulimab as the first PD-1 inhibitor combined with chemo for untreated ES-SCLC.

Clinical trial identification

NCT04063163.

Editorial acknowledgement

Shiqi Zhong and Chen Hu of Shanghai Henlius Biotech, Inc.

Legal entity responsible for the study

Shanghai Henlius Biotech, Inc.

Funding

Shanghai Henlius Biotech, Inc.

Disclosure

W. Kang, Q. Wang, J. Zhu: Financial Interests, Personal, Full or part-time Employment: Shanghai Henlius Biotech, Inc. All other authors have declared no conflicts of interest.