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).
Zhi Peng, Jufeng Wang, Yanqiao Zhang et al.
✦ AI-curated · Sources linked
In 30 seconds
RELIGHT was a randomized, double-blind, phase III trial of first-line retlirafusp alfa plus capecitabine and oxaliplatin (CAPOX) versus placebo plus CAPOX in 731 patients with previously untreated, unresectable, locally advanced or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma. Overall survival was significantly longer with retlirafusp alfa in both the PD-L1 CPS ≥5 group (median 16.8 vs 10.4 months; HR 0.53) and the intention-to-treat population (15.8 vs 11.2 months; HR 0.66). Grade ≥3 treatment-related adverse events were broadly comparable between groups.
Key findings
- In patients with PD-L1 CPS ≥5, median overall survival was 16.8 vs 10.4 months (HR 0.53 [95% CI, 0.40-0.68]; one-sided P < .0001).
- In the intention-to-treat population, median overall survival was 15.8 vs 11.2 months (HR 0.66 [95% CI, 0.53-0.81]; one-sided P < .0001).
- Median progression-free survival was 7.6 v 5.5 months for PD-L1 CPS ≥5 (HR 0.52) and 7.0 v 5.5 months in the intention-to-treat population (HR 0.57).
- Grade ≥3 treatment-related adverse events occurred in 62.6% (228 of 364) with retlirafusp alfa plus CAPOX and 59.0% (216 of 366) with placebo plus CAPOX.
Why it matters
The trial reports improved overall survival when retlirafusp alfa is added to CAPOX in this advanced HER2-negative cancer population, including in the intention-to-treat analysis. The survival findings and broadly comparable rates of severe treatment-related adverse events are relevant to evaluating first-line treatment options, while the comparator context limits direct comparison with current immunotherapy-containing regimens.
What to keep in mind
The comparator was chemotherapy alone; the protocol was finalized before PD-1 inhibitor plus chemotherapy became the approved standard-of-care regimen in China.