Retlirafusp alfa plus chemotherapy beats chemo alone in HER2-negative gastric cancer
Primary endpointOverall survival (OS)
Median (months) · In patients with PD-L1 CPS ≥5
Where these numbers come from
“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 < 0.0001) 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 < 0.0001).”
The publication
In a phase III trial, adding retlirafusp alfa to chemotherapy improved overall survival for patients with unresectable, locally advanced or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma. Among patients with PD-L1 CPS ≥5, median overall survival was 16.8 months with retlirafusp alfa plus chemotherapy compared with 10.4 months with placebo plus chemotherapy.
Who the findings apply to
The trial enrolled patients with previously untreated, unresectable, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
Participants were required to have human epidermal growth factor receptor 2 (HER2)-negative disease.
The primary analysis focused on patients with a PD-L1 combined positive score (CPS) of 5 or higher.
Patients were randomly assigned to receive retlirafusp alfa or placebo intravenously every 3 weeks in addition to capecitabine and oxaliplatin.
Why this matters
The study demonstrates that retlirafusp alfa, an anti-PD-L1/transforming growth factor-β bispecific antibody, provides a significant survival benefit when added to capecitabine and oxaliplatin. This offers a new first-line treatment option for a population with limited effective therapies, although the comparison was against chemotherapy alone rather than the current standard of care involving PD-1 inhibitors.
What the study found
In patients with PD-L1 CPS ≥5, median overall survival was 16.8 months with retlirafusp alfa plus chemotherapy versus 10.4 months with placebo plus chemotherapy.
The stratified hazard ratio for overall survival in the PD-L1 CPS ≥5 group was 0.53 (95% CI, 0.40-0.68), with a one-sided P value less than .0001.
In the intention-to-treat analysis set, median overall survival was 15.8 months with retlirafusp alfa plus chemotherapy versus 11.2 months with placebo plus chemotherapy.
The stratified hazard ratio for overall survival in the intention-to-treat set was 0.66 (95% CI, 0.53-0.81), with a one-sided P value less than .0001.
Progression-free survival was also improved, with a median of 7.6 months versus 5.5 months in the PD-L1 CPS ≥5 group and 7.0 months versus 5.5 months in the intention-to-treat set.
What the result does not establish
Grade 3 or higher treatment-related adverse events were comparable between groups, occurring in 62.6% of patients receiving retlirafusp alfa plus chemotherapy and 59.0% of those receiving placebo plus chemotherapy.
A key limitation is that the control arm received chemotherapy alone, as the study protocol was finalized before PD-1 inhibitor plus chemotherapy became the approved standard-of-care regimen in China.
The study was a randomized, double-blind, phase III trial, but the comparator does not reflect current standard-of-care practices in some regions.
Authors’ 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.”
Study and sources
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)
Randomised trial · Phase 3 · Journal of clinical oncology · 2026-09-24
Sources and limitations
- PubMed record PMID 42784781 (PubMed / NLM · 2026-09-25)
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