IAP拮抗剂APG-1387联合nab-紫杉醇和吉西他滨治疗难治性转移性胰腺癌的一期临床试验。

IF 10.6 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-09-19 DOI:10.1016/j.xcrm.2025.102364

Si Shi, Jian Zhang, Rujiao Liu, Shuiping Gao, Jin Xu, Wei Wang, Miaoyan Wei, Jialin Li, Chen Liu, Xiaowu Xu, Wentao Pan, Xiaohong Tian, Lichuang Men, Hengbang Wang, Zhiyan Liang, Min Zhu, Dajun Yang, Yifan Zhai, XianJun Yu

{"title":"IAP拮抗剂APG-1387联合nab-紫杉醇和吉西他滨治疗难治性转移性胰腺癌的一期临床试验。","authors":"Si Shi, Jian Zhang, Rujiao Liu, Shuiping Gao, Jin Xu, Wei Wang, Miaoyan Wei, Jialin Li, Chen Liu, Xiaowu Xu, Wentao Pan, Xiaohong Tian, Lichuang Men, Hengbang Wang, Zhiyan Liang, Min Zhu, Dajun Yang, Yifan Zhai, XianJun Yu","doi":"10.1016/j.xcrm.2025.102364","DOIUrl":null,"url":null,"abstract":"Advanced pancreatic cancer presents dismal survival with limited effective, well-tolerated options beyond chemotherapy. This phase 1 trial evaluates the safety, tolerability, and efficacy of bivalent IAP antagonist APG-1387 with nab-paclitaxel and gemcitabine (AG) in patients failing or intolerant to standard care. In 28-day cycles, patients receive intravenous infusions of APG-1387 (20, 30, or 45 mg) on days 1, 8, 15, and 22, and nab-paclitaxel (125 mg/m2) and gemcitabine (1,000 mg/m2) on days 1, 8, and 15, with dose-limiting toxicity (DLT) as the primary endpoint per NCI CTCAE v5.0. Of 28 screened, 21 are enrolled; one grade 4 DLT recovers within 3 days, and 9 (42.9%) experience grade ≥3 treatment-related adverse events, mostly AG-related bone marrow toxicities. Among 15 efficacy-evaluable patients, 3 achieve partial responses, including 1 (33%) without prior AG. APG-1387 with AG demonstrates tolerability and encouraging posterior-line antitumor effects in AG-naive patients (NCT04643405).","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102364"},"PeriodicalIF":10.6000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A phase 1 trial of APG-1387, an IAP antagonist, with nab-paclitaxel and gemcitabine in patients with refractory metastatic pancreatic cancer.\",\"authors\":\"Si Shi, Jian Zhang, Rujiao Liu, Shuiping Gao, Jin Xu, Wei Wang, Miaoyan Wei, Jialin Li, Chen Liu, Xiaowu Xu, Wentao Pan, Xiaohong Tian, Lichuang Men, Hengbang Wang, Zhiyan Liang, Min Zhu, Dajun Yang, Yifan Zhai, XianJun Yu\",\"doi\":\"10.1016/j.xcrm.2025.102364\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Advanced pancreatic cancer presents dismal survival with limited effective, well-tolerated options beyond chemotherapy. This phase 1 trial evaluates the safety, tolerability, and efficacy of bivalent IAP antagonist APG-1387 with nab-paclitaxel and gemcitabine (AG) in patients failing or intolerant to standard care. In 28-day cycles, patients receive intravenous infusions of APG-1387 (20, 30, or 45 mg) on days 1, 8, 15, and 22, and nab-paclitaxel (125 mg/m2) and gemcitabine (1,000 mg/m2) on days 1, 8, and 15, with dose-limiting toxicity (DLT) as the primary endpoint per NCI CTCAE v5.0. Of 28 screened, 21 are enrolled; one grade 4 DLT recovers within 3 days, and 9 (42.9%) experience grade ≥3 treatment-related adverse events, mostly AG-related bone marrow toxicities. Among 15 efficacy-evaluable patients, 3 achieve partial responses, including 1 (33%) without prior AG. APG-1387 with AG demonstrates tolerability and encouraging posterior-line antitumor effects in AG-naive patients (NCT04643405).\",\"PeriodicalId\":9822,\"journal\":{\"name\":\"Cell Reports Medicine\",\"volume\":\" \",\"pages\":\"102364\"},\"PeriodicalIF\":10.6000,\"publicationDate\":\"2025-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Reports Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.xcrm.2025.102364\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Reports Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.xcrm.2025.102364","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

晚期胰腺癌生存率低，除化疗外，有效且耐受性良好的选择有限。这项i期试验评估了双价IAP拮抗剂APG-1387与nab-紫杉醇和吉西他滨（AG）联合治疗标准治疗失败或不耐受患者的安全性、耐受性和有效性。在28天的周期中，患者在第1、8、15和22天静脉输注APG-1387(20、30或45 mg)，并在第1、8和15天静脉输注nab-紫杉醇（125 mg/m2）和吉西他滨（1000 mg/m2），根据NCI CTCAE v5.0，以剂量限制性毒性（DLT）作为主要终点。在筛选的28人中，有21人入选；1例4级DLT患者在3天内康复，9例（42.9%）出现≥3级治疗相关不良事件，主要是ag相关的骨髓毒性。在15例可评估疗效的患者中，3例达到部分缓解，其中1例（33%）没有既往的AG。APG-1387在AG初发患者中显示耐受性和令人鼓舞的后线抗肿瘤作用（NCT04643405）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

A phase 1 trial of APG-1387, an IAP antagonist, with nab-paclitaxel and gemcitabine in patients with refractory metastatic pancreatic cancer.

Advanced pancreatic cancer presents dismal survival with limited effective, well-tolerated options beyond chemotherapy. This phase 1 trial evaluates the safety, tolerability, and efficacy of bivalent IAP antagonist APG-1387 with nab-paclitaxel and gemcitabine (AG) in patients failing or intolerant to standard care. In 28-day cycles, patients receive intravenous infusions of APG-1387 (20, 30, or 45 mg) on days 1, 8, 15, and 22, and nab-paclitaxel (125 mg/m²) and gemcitabine (1,000 mg/m²) on days 1, 8, and 15, with dose-limiting toxicity (DLT) as the primary endpoint per NCI CTCAE v5.0. Of 28 screened, 21 are enrolled; one grade 4 DLT recovers within 3 days, and 9 (42.9%) experience grade ≥3 treatment-related adverse events, mostly AG-related bone marrow toxicities. Among 15 efficacy-evaluable patients, 3 achieve partial responses, including 1 (33%) without prior AG. APG-1387 with AG demonstrates tolerability and encouraging posterior-line antitumor effects in AG-naive patients (NCT04643405).

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.