Gastric Cancer Center, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Abdominal Oncology Ward, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Front Immunol. 2024 Nov 13;15:1431957. doi: 10.3389/fimmu.2024.1431957. eCollection 2024.
Recently, the clinical benefits of neoadjuvant chemotherapy combined with immunotherapy have been observed in patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer; however, the pathological complete response (pCR) and long-term survival rates are still unsatisfactory. The aim of this study is to investigate the efficacy and safety of chemotherapy combined with tislelizumab and low-dose radiation therapy (LDRT) for the neoadjuvant treatment of locally advanced G/GEJ cancer.
This is a prospective, multicenter, single-arm, phase Ib/II trial. In the phase Ib study, 5 patients will be enrolled in each treatment group with different radiation doses. In the phase II study, a total of 44 patients will be enrolled. Eligible patients will be registered and receive three cycles of SOX regimen chemotherapy (S-1: 40-60 mg Bid, d1-14, q3w; oxaliplatin: 130 mg/m, iv drip, d1, q3w) plus tislelizumab (200 mg, iv drip, d1, q3w). Simultaneously, LDRT will be planned and administered after the first cycle of systemic therapy. Radical D2 gastrectomy will be performed 4-6 weeks after the last administration of chemotherapy plus tislelizumab. The primary endpoint of phase Ib study is to determine the optimal radiation dose for phase II study. The primary endpoint of phase II is the pCR rate. The secondary endpoints include R0 resection rate, major pathological response (MPR) rate, 2-year event-free survival (EFS) rate, 2-year overall survival (OS) rate and safety profile. Moreover, we will also explore potential molecular markers for predicting the benefit and safety of this neoadjuvant regimen. Written informed consent should be provided by all patients enrolled in the study. The study protocol was approved by the independent ethics committee at each institution.
This is the first study to explore the efficacy and safety of neoadjuvant chemotherapy combined with tislelizumab and LDRT in G/GEJ cancer patients, the results of which may provide novel treatment strategy for patients with locally advanced G/GEJ adenocarcinoma.
ClinicalTrials.Gov, identifier NCT06266871.
最近，新辅助化疗联合免疫疗法在局部晚期胃或胃食管交界处（G/GEJ）癌患者中观察到了临床获益，但病理完全缓解（pCR）率和长期生存率仍不理想。本研究旨在探讨替雷利珠单抗联合低剂量放疗（LDRT）新辅助治疗局部晚期 G/GEJ 癌的疗效和安全性。
这是一项前瞻性、多中心、单臂、Ib/II 期研究。在 Ib 期研究中，每组治疗将纳入 5 例患者，采用不同的放射剂量。在 II 期研究中，共纳入 44 例患者。符合条件的患者将被登记并接受三周期 SOX 方案化疗（S-1：40-60 mg Bid，d1-14，q3w；奥沙利铂：130 mg/m2，iv 滴注，d1，q3w）加替雷利珠单抗（200 mg，iv 滴注，d1，q3w）。同时，在系统治疗的第一周期后计划并进行 LDRT。化疗加替雷利珠单抗末次给药后 4-6 周行根治性 D2 胃切除术。Ib 期研究的主要终点是确定 II 期研究的最佳放射剂量。II 期研究的主要终点是 pCR 率。次要终点包括 R0 切除率、主要病理缓解（MPR）率、2 年无事件生存率（EFS）率、2 年总生存率（OS）率和安全性。此外，我们还将探索预测该新辅助方案获益和安全性的潜在分子标志物。所有入组患者均应签署书面知情同意书。该研究方案经各机构独立伦理委员会批准。
这是第一项探讨替雷利珠单抗联合替雷利珠单抗和 LDRT 在 G/GEJ 癌患者中的疗效和安全性的研究，其结果可能为局部晚期 G/GEJ 腺癌患者提供新的治疗策略。
ClinicalTrials.Gov，标识符 NCT06266871。
