S-588410 是一种癌症肽疫苗 (CPV)，包含来自五种癌症睾丸抗原的五种 HLA-A*24:02 限制性肽。在一项 2 期研究中，S-588410 对尿路上皮癌患者具有良好的耐受性并表现出抗肿瘤功效。因此，我们的目的是评估 S-588410 在完全切除的食管鳞状细胞癌 (ESCC) 患者中的疗效、免疫反应和安全性。这项 3 期研究涉及 HLA-A*24:02 阳性且淋巴结转移的患者接受新辅助治疗并随后进行根治性切除的转移阳性食管鳞癌。随机分组后，患者皮下注射 S-588410 和安慰剂（均用 Montanide™ ISA 51VG 乳化）。主要终点是无复发生存期（RFS）。次要终点是总生存期 (OS)、细胞毒性 T 淋巴细胞 (CTL) 诱导和安全性。使用 Fleming-Harrington 类权重的单侧加权对数秩检验检验统计显着性。总共 276 名患者被随机分组​​（N = 138/组）。 S-588410 组和安慰剂组的中位 RFS 分别为 84.3 周和 84.1 周 (P = 0.8156)，而中位 OS 分别为 236.3 周，未达到 (P = 0.6533)。在 12 周内接受 S-588410 治疗的 132/134 (98.5%) 患者中观察到 CTL 诱导。注射部位反应（137/140 名患者 [97.9%]）是 S-588410 组中最常见的治疗引起的不良事件。在接受 S-588410 治疗的患有上胸部 ESCC、3 级注射部位反应或高 CTL 强度的患者中观察到生存期延长。S-588410 诱导免疫反应并具有可接受的安全性，但未能达到主要终点。高 CTL 诱导率和强度可能对于延长未来 CPV 发育过程中的生存期至关重要。© 2024。作者。

S-588410, a cancer peptide vaccine (CPV), comprises five HLA-A*24:02-restricted peptides from five cancer-testis antigens. In a phase 2 study, S-588410 was well-tolerated and exhibited antitumor efficacy in patients with urothelial cancer. Therefore, we aimed to evaluate the efficacy, immune response, and safety of S-588410 in patients with completely resected esophageal squamous cell carcinoma (ESCC).This phase 3 study involved patients with HLA-A*24:02-positive and lymph node metastasis-positive ESCC who received neoadjuvant therapy followed by curative resection. After randomization, patients were administered S-588410 and placebo (both emulsified with Montanide™ ISA 51VG) subcutaneously. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were overall survival (OS), cytotoxic T-lymphocyte (CTL) induction, and safety. Statistical significance was tested using the one-sided weighted log-rank test with the Fleming-Harrington class of weights.A total of 276 patients were randomized (N = 138/group). The median RFS was 84.3 and 84.1 weeks in the S-588410 and placebo groups, respectively (P = 0.8156), whereas the median OS was 236.3 weeks and not reached, respectively (P = 0.6533). CTL induction was observed in 132/134 (98.5%) patients who received S-588410 within 12 weeks. Injection site reactions (137/140 patients [97.9%]) were the most frequent treatment-emergent adverse events in the S-588410 group. Prolonged survival was observed in S-588410-treated patients with upper thoracic ESCC, grade 3 injection-site reactions, or high CTL intensity.S-588410 induced immune response and had acceptable safety but failed to reach the primary endpoint. A high CTL induction rate and intensity may be critical for prolonging survival during future CPV development.© 2024. The Author(s).