Retlirafusp Alfa Plus CAPOX Extends Gastric Cancer Survival

Adding retlirafusp alfa to capecitabine and oxaliplatin (CAPOX) prolonged overall survival compared with placebo plus CAPOX in patients with previously untreated, unresectable locally advanced or metastatic, HER2-negative gastric or gastroesophageal junction adenocarcinoma. The phase 3 RELIGHT findings were published in the Journal of Clinical Oncology.

Retlirafusp alfa is a bispecific antibody targeting PD-L1 and transforming growth factor-β. In the randomized, double-blind trial, 731 patients were assigned to intravenous retlirafusp alfa or placebo every 3 weeks, each with CAPOX. The primary endpoint was overall survival in patients with a PD-L1 combined positive score (CPS) of at least 5 and in the intention-to-treat population.

Among patients with a CPS of at least 5, median overall survival was 16.8 months with retlirafusp alfa plus CAPOX versus 10.4 months with placebo plus CAPOX (hazard ratio [HR], 0.53; 95% CI, 0.40-0.68). In the intention-to-treat population, median overall survival was 15.8 versus 11.2 months, respectively (HR, 0.66; 95% CI, 0.53-0.81). Both comparisons had a one-sided P value below .0001.

Median progression-free survival was 7.6 versus 5.5 months in patients with a CPS of at least 5 and 7.0 versus 5.5 months in the intention-to-treat population, favoring retlirafusp alfa. Grade 3 or higher treatment-related adverse events occurred in 62.6% (228 of 364) of patients receiving retlirafusp alfa plus CAPOX and 59.0% (216 of 366) receiving placebo plus CAPOX.

The study was supported by Jiangsu Hengrui Pharmaceuticals Co, Ltd. The authors identified the chemotherapy-only comparator as a key limitation: the protocol was finalized before PD-1 inhibitor plus chemotherapy became the approved standard treatment in China.

Source: Peng Z, Wang J, Zhang Y, et al. First-line retlirafusp alfa plus chemotherapy for human epidermal growth factor receptor 2–negative gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase III study (RELIGHT). J Clin Oncol. Published online September 24, 2026. doi:10.1200/JCO-25-02933