Adding the PD-1 antibody serplulimab to standard chemotherapy before and after stomach-cancer surgery delayed relapse, according to ASTRUM-006, a randomised, double-blind, multicentre phase 3 trial published in The Lancet. The result extends an already established chemo-immunotherapy strategy to a biomarker-selected group: patients whose tumours express PD-L1.

Patients were screened at 75 hospitals in China and Thailand between November 2019 and April 2024. Of 1646 screened, 588 with resectable, PD-L1-positive gastric or gastro-oesophageal junction adenocarcinoma — a combined positive score (CPS) of 5 or higher — were randomly assigned, all at 57 hospitals in China. The serplulimab group (n=292) received neoadjuvant serplulimab plus S-1 and oxaliplatin (SOX), then adjuvant serplulimab; the placebo group (n=296) received placebo plus SOX, then adjuvant SOX alone.

What the trial found

The primary endpoint was investigator-assessed event-free survival — time from randomisation to progression, local or distant recurrence, a new malignancy, or death. Following a prespecified hierarchical testing sequence, efficacy was evaluated first in the most PD-L1-rich patients (CPS ≥10) and then in the full intention-to-treat (CPS ≥5) population.

In the CPS ≥10 population, the first prespecified analysis, median event-free survival was not reached with serplulimab versus 42.0 months with placebo (hazard ratio 0.65, 95% CI 0.47–0.90; p=0.0082). In the intention-to-treat (CPS ≥5) population, tested next, median event-free survival was again not reached with serplulimab versus 35.9 months with placebo (hazard ratio 0.73, 95% CI 0.56–0.94; p=0.015).

Grade 3-or-worse treatment-related adverse events were less common with serplulimab — 47% versus 59% — and fewer patients discontinued treatment.

The authors note that overall survival data are not yet mature and that extended follow-up “is warranted to confirm a survival advantage.” Longer event-free survival is a meaningful but intermediate signal; whether it translates into patients living longer remains unproven. And although patients were screened in China and Thailand, every randomised patient was enrolled in China, so applicability to other populations is untested. The study was funded by Shanghai Henlius Biotech, which makes serplulimab.