69O - First-line serplulimab versus placebo in combination with chemotherapy in PD-L1-positive oesophageal squamous cell carcinoma (ASTRUM-007): A randomised, double-blind, multicentre phase III study

Background

Immune checkpoint inhibitor plus chemotherapy (chemo) as first-line treatment improves efficacy in oesophageal squamous cell carcinoma (ESCC) patients, yet the optimal target population for this combination therapy is uncertain, and the treatment outcomes are still unsatisfactory. Efficacy and safety of serplulimab, a novel anti-PD-1 antibody, were evaluated in combination with chemo in patients with previously untreated, advanced, PD-L1-positive (CPS ≥1) ESCC.

Methods

Eligible patients were enrolled in this double-blind phase 3 trial (NCT03958890) and randomised 2:1 to receive serplulimab 3 mg/kg or placebo combined with cisplatin 50 mg/m² and 5-fluorouracil 1200 mg/m² daily on days 1–2 intravenously every 2 weeks. Randomisation was stratified by PD-L1 expression levels, age, and disease status. Co-primary endpoints were PFS assessed by the independent radiology review committee and OS in the ITT population.

Results

Between June 19, 2019, and Dec 17, 2021, 551 patients were randomised to receive serplulimab plus chemo (n=368) or placebo plus chemo (n=183). Median follow-up duration was 14.9 months. Median PFS (final analysis) was significantly longer in serplulimab plus chemo group (5.8 months [95% CI 5.7–6.9]) than that in placebo plus chemo group (5.3 months [95% CI 4.3–5.6]; HR 0.60, 95% CI 0.48–0.75; p<0.0001). Median OS (interim analysis) was also significantly improved with the addition of serplulimab (15.3 months [95% CI 14.0–18.6] versus 11.8 months [95% CI 9.7–14.0]; HR 0.68, 95% CI 0.53–0.87; p=0.0020). Grade ≥3 treatment-related AEs occurred in 201 (52.6%) patients receiving serplulimab plus chemo and in 81 (48.2%) receiving placebo plus chemo, with deaths due to treatment-related AEs occurring in 11 (2.9%) and 3 (1.8%) patients in the respective groups.

Conclusions

Serplulimab in combination with chemo administered every 2 weeks significantly improved PFS (final) and OS (interim) compared with chemo alone in first-line therapy of PD-L1-positive advanced ESCC, which can be considered as a new standard option for this patient population.

Clinical trial identification

CTR20190911, NCT03958890.

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

J. Huang: Non-Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme (MSD), Roche. Q. Wang: Financial Interests, Personal, Full or part-time Employment: Shanghai Henlius Biotech, Inc. J. Zhu: Financial Interests, Personal, Full or part-time Employment: Shanghai Henlius Biotech, Inc. All other authors have declared no conflicts of interest.