retlirafusp alfa（抗 PD-L1/TGF-β 双特异性抗体）联合化疗一线治疗 HER2 阴性胃或胃食管结合部腺癌：随机双盲 III 期研究（RELIGHT）
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)
研究针对未经治疗、不可切除的局部晚期或转移性 HER2 阴性胃或胃食管结合部腺癌患者。731 名患者按 1:1 随机接受 retlirafusp alfa（一种同时靶向 PD-L1 和转化生长因子-β 的双特异性抗体）或安慰剂，联合卡培他滨加奥沙利铂（CAPOX）化疗，每 3 周静脉给药。结果显示，在 PD-L1 联合阳性评分（CPS）≥5 的患者中，中位总生存期为 16.8 个月对 10.4 个月；在全体意向治疗人群中为 15.8 个月对 11.2 个月，均具统计学显著获益。无进展生存期也呈一致获益，两组严重不良事件发生率相近。该方案有望成为这类患者的一线治疗选择；局限在于对照为单纯化疗，因方案定稿时 PD-1 抑制剂联合化疗尚未成为中国标准治疗。
为什么推荐给您：双特异性抗体联合化疗的大型 III 期阳性结果，但属已知免疫联合化疗策略的扩展
不需要生物学背景，多打比方
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摘要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.