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)
In brief
Retlirafusp plus chemotherapy adds 4.6 months to median survival in advanced gastric cancer
In this phase III trial, 731 patients receiving retlirafusp plus chemotherapy lived a median 15.8 months, compared with 11.2 months on chemotherapy alone; the difference was larger among patients with higher PD-L1 scores. Severe treatment-related side effects were similar between groups, but the trial did not compare the combination with today's standard immunotherapy-plus-chemotherapy regimen in China.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 24 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Zhi Peng, Jufeng Wang, Yanqiao Zhang, Hongli Li, Qun Zhao, Xiaodong Zhu, et al.
- PMID
- 42784781
- DOI
- 10.1200/JCO-25-02933
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 25 September 2026): Phase III RCT of retlirafusp + CAPOX in gastric cancer
Abstract
PURPOSE: To evaluate retlirafusp alfa (an anti-PD-L1/transforming growth factor-β bispecific antibody) plus standard chemotherapy as first-line treatment for unresectable, locally advanced or metastatic, human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction adenocarcinoma in the first-line setting. METHODS: In this randomized, double-blind (RELIGHT), phase III study, 731 patients with previously untreated, unresectable, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma were randomly assigned (1:1) to receive retlirafusp alfa or placebo intravenously every 3 weeks plus capecitabine and oxaliplatin (CAPOX). The primary end point was overall survival (OS), assessed in patients with PD-L1 combined positive score (CPS) ≥5 and the intention-to-treat analysis set. RESULTS: Retlirafusp alfa plus CAPOX significantly prolonged OS versus placebo plus CAPOX in both patients with PD-L1 CPS ≥5 (median, 16.8 vs 10.4 months; stratified hazard ratio [HR], 0.53 [95% CI, 0.40-0.68]; one-sided P < .0001) and the intention-to-treat analysis set (median, 15.8 vs 11.2 months; stratified HR, 0.66 [95% CI, 0.53-0.81]; one-sided P < .0001). Progression-free survival benefit was observed with retlirafusp alfa plus CAPOX versus placebo plus CAPOX in both patients with PD-L1 CPS ≥5 (median, 7.6 v 5.5 months; stratified HR, 0.52 [95% CI, 0.42 to 0.66]) and the intention-to-treat analysis set (median, 7.0 v 5.5 months; stratified HR, 0.57 [95% CI, 0.48 to 0.69]). Grade ≥3 treatment-related adverse events were generally comparable between patients treated with retlirafusp alfa plus CAPOX (62.6% [228 of 364]) and those treated with placebo plus CAPOX (59.0% [216 of 366]). CONCLUSION: Retlirafusp alfa plus CAPOX represents a first-line treatment option for unresectable, locally advanced or metastatic, HER2-negative gastric or gastroesophageal junction adenocarcinoma. A key limitation is that chemotherapy alone served as the comparator, given that the study protocol was finalized before PD-1 inhibitor plus chemotherapy became the approved standard-of-care regimen in China.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.