Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1–14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8–89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).

晚期胃癌患者通常面临严峻的预后。这项 1a 期（剂量递增）和 1b 期（剂量扩展）研究调查了一线卡瑞利珠单抗联合阿帕替尼和化疗治疗晚期胃或胃食管交界腺癌的安全性和有效性。主要终点包括 1a 期的最大耐受剂量 (MTD) 以及 1a 期和 1b 期的客观缓解率 (ORR)。 1a 期测试了卡瑞利珠单抗、阿帕替尼、奥沙利铂和 S-1 的三种剂量方案。剂量方案 1：第 1 天卡瑞利珠单抗 200 mg，每隔一天阿帕替尼 250 mg，第 1 天奥沙利铂 100 mg/m²，第 1-14 天 S-1 40 mg 每天两次。剂量方案2：与剂量方案1相同，但奥沙利铂130mg/m²。剂量方案3：与剂量方案2相同，但阿帕替尼每天250mg。共纳入 34 名患者（1a 期 9 名，1b 期 25 名）。没有发生剂量限制性毒性，因此没有确定 MTD。剂量 3 设定为推荐的 2 期剂量，并在 1b 期施用。确认的 ORR 为 76.5% (95% CI 58.8–89.3)。中位无进展生存期为 8.4 个月（95% CI 5.9 - 无法评估 [NE]），中位总生存期 (OS) 尚未成熟 (11.6-NE)。十名患者经过治疗和多学科团队评估后接受了手术。在 24 名未接受手术的患者中，中位 OS 为 19.6 个月 (7.8-NE)。 18 名患者 (52.9%) 出现 ≥ 3 级治疗引起的不良事件。卡瑞利珠单抗联合阿帕替尼和化疗对于未经治疗的晚期胃癌显示出良好的临床结果和可控的安全性 (ChiCTR2000034109)。