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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).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>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\u2122 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\u2013Harrington class of weights.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A total of 276 patients were randomized (<jats:italic>N<\/jats:italic>\u2009=\u2009138\/group). The median RFS was 84.3 and 84.1\u00a0weeks in the S-588410 and placebo groups, respectively (<jats:italic>P<\/jats:italic>\u2009=\u20090.8156), whereas the median OS was 236.3\u00a0weeks and not reached, respectively (<jats:italic>P<\/jats:italic>\u2009=\u20090.6533). CTL induction was observed in 132\/134 (98.5%) patients who received S-588410 within 12\u00a0weeks. 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10388-024-01072-w","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T13:01:56Z","timestamp":1720702916000},"page":"447-455","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A phase 3, randomized, double-blind, multicenter, placebo-controlled study of S-588410, a five-peptide cancer vaccine as an adjuvant therapy after curative resection in patients with esophageal squamous cell carcinoma"],"prefix":"10.1007","volume":"21","author":[{"given":"Tomoki","family":"Makino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Miyata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4025-8113","authenticated-orcid":false,"given":"Takushi","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Kitagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Muro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hyun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Hikichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Igarashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motofumi","family":"Iguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhide","family":"Masaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Yano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Doki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"1072_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, et al. 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YK reports grants to his institution from Chugai Pharmaceutical, Taiho Pharmaceutical, Asahi Kasei Pharma, Otsuka Pharmaceutical, Tsumura, Kaken Pharmaceutical, Sumitomo Pharma, Eisai, Otsuka Pharmaceutical Factory, Kyowa Kirin, Takeda Pharmaceutical, Teijin Pharma, and Kowa; and personal fee from Asahi Kasei Pharma, Astra Zeneca, Ethicon, Ono Pharmaceutical, Otsuka Pharmaceutical Factory, Olympus, Cardinal Health, Shionogi & Co., Ltd., Taiho Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, MSD, Smith & Nephew, Kaken Pharmaceutical, Aska Pharmaceutical, Miyarisan Pharmaceutical, Toray Industries, Daiichi Sankyo, Chugai Foundation for Innovation Drug Discovery Science, Nippon Kayaku, EA Pharma, Intuitive Surgical, Takeda Pharmaceutical, Sysmex, Tsumura, AI Medical Service, Kowa, and Eisai; and Joint Research Laboratory for Development and Education of Innovative Medical Technology for Sysmex and Medicaroid; and Editor in Chief of Annals of Gastroenterological Surgery issued by The Japanese Society of Gastroenterological Surgery. KM reports honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, Eli Lilly, Daiichi Sankyo, Taiho Pharmaceutical, Takeda Pharmaceutical and MSD; and research funding from PRA Health Science, Astellas, Novartis Pharma, Amgen, Sanofi, Taiho Pharmaceutical, MSD, Chugai Pharmaceutical and Paraxel International. YD reports that his institution received a research grant from Shionogi & Co., Ltd outside of this clinical study. JP is an employee of OncoTherapy Science Inc. THi is an employee of OncoTherapy Science, Inc. and an assigned employee of Cancer Precision Medicine, Inc, and has stock options of OncoTherapy Science, Inc.; and patent pending (WO 2022\/149295). THa is an employee of Shionogi & Co., Ltd., and has stocks of Shionogi & Co., Ltd. YM was an employee of Shionogi & Co., Ltd. when the study was conducted, and has minor stocks of Shionogi & Co., Ltd.; and reports participation on Data safety Monitoring Board and Advisory Board that Shionogi & Co., Ltd. held. KI, and MI were also employees of Shionogi & Co., Ltd. when the study was conducted. All other authors declare that they have no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Informed consent or substitute for it was obtained from all patients for being included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}