Domvanalimab and zimberelimab in advanced gastric, gastroesophageal junction or esophageal cancer: a phase 2 trial.

Here we report the EDGE-Gastric study, an ongoing, multicenter, international, phase 2 study with three cohorts, one in the first-line setting (cohort A) and two in the second-line or greater setting (cohorts B and C).

我们报告了 EDGE-Gastric 研究，这是一项正在进行的多中心、国际、二期临床试验，包含三个队列，一个在一线治疗设置中（队列 A），两个在二线或更高线治疗设置中（队列 B 和 C）。

Cohort A comprises four arms: two nonrandomized (A1 and A2) and two randomized (A3 and A4).

队列A包含四个组别：两个非随机组（A1和A2）和两个随机组（A3和A4）。

In arm A1, presented here, dual blockade of TIGIT and PD-1 with domvanalimab (Fc-silent anti-TIGIT) and zimberelimab (anti-PD-1) plus oxaliplatin, leucovorin, fluorouracil (FOLFOX) was evaluated in patients with previously untreated advanced HER2-negative gastric, gastroesophageal junction or esophageal adenocarcinoma.

在本研究中介绍的A1组中，使用domvanalimab（Fc静默抗TIGIT）和zimberelimab（抗PD-1）双重阻断TIGIT和PD-1，联合奥沙利铂、亚叶酸钙和氟尿嘧啶（FOLFOX）方案，评估了之前未接受治疗的晚期HER2阴性胃癌、胃食管交界处或食管腺癌患者。

Among 41 treated patients, the confirmed objective response ratewas 59% (90% confidence interval(CI) 44.5-71.6%), median progression-free survivalwas 12.9 months (90% CI 9.8-14.6 months) and median overall survivalwas 26.7 months (90% CI 18.4 months to not estimable (NE)).

在41名接受治疗的患者中，确认的客观缓解率为59%（90%置信区间（CI）44.5-71.6%），无进展生存期中位数为12.9个月（90% CI 9.8-14.6个月），总生存期中位数为26.7个月（90% CI 18.4个月至无法估计（NE））。

In patients with tumor area positivity ≥1% (PD-L1 positive) and tumor area positivity ≥5% (PD-L1 high), respectively, the objective response ratewas 62% (90% CI 45.1-77.1%) and 69% (90% CI 45.2-86.8%), median progression-free survivalwas 13.2 months (90% CI 11.3-15.2 months) and 14.5 months (90% CI 11.3 months-NE), and median overall survivalwas 26.7 months (90% CI 19.5 months-NE) and not reached (90% CI 17.4 months-NE).

在肿瘤面积阳性≥1%（PD-L1阳性）和肿瘤面积阳性≥5%（PD-L1高表达）的患者中，客观缓解率分别为62%（90% CI 45.1-77.1%）和69%（90% CI 45.2-86.8%），无进展生存期中位数分别为13.2个月（90% CI 11.3-15.2个月）和14.5个月（90% CI 11.3个月-NE），总生存期中位数分别为26.7个月（90% CI 19.5个月-NE）和未达到（90% CI 17.4个月-NE）。

Immune-related adverse events were reported in 27% of patients; the safety profile was consistent with that reported for anti-PD-1 plus platinum-based chemotherapy.

27%的患者报告了免疫相关不良事件；安全性特征与抗PD-1联合铂类化疗所报告的一致。

Dual TIGIT and PD-1 blockade with domvanalimab and zimberelimab plus chemotherapy demonstrated encouraging efficacy, and the regimen is being evaluated in the phase 3 STAR-221 trial. ClinicalTrials.gov identifier: NCT05329766 .

domvanalimab和zimberelimab联合化疗的双重TIGIT和PD-1阻断显示出令人鼓舞的疗效，该方案正在第3期STAR-221试验中进行评估。ClinicalTrials.gov注册号：NCT05329766。