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/m<sup>2</sup>) and gemcitabine (1,000 mg/m<sup>2</sup>) 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).
Authors
- Yifan Zhai
- Hengbang Wang (ORCID: https://orcid.org/0000-0003-3740-9056)
- Jian Zhang (ORCID: https://orcid.org/0000-0002-5982-419X)
- Wei Wang (ORCID: https://orcid.org/0000-0002-9616-1145)
- Zhiyan Liang (ORCID: https://orcid.org/0000-0002-0404-1243)
- Jin Xu (ORCID: https://orcid.org/0000-0002-5270-0223)
- Shuiping Gao (ORCID: https://orcid.org/0000-0002-9895-1650)
- Wentao Pan (ORCID: https://orcid.org/0000-0001-5352-1596)
- Rujiao Liu (ORCID: https://orcid.org/0000-0002-6803-0594)
- Si Shi (ORCID: https://orcid.org/0000-0002-6652-0629)
- Dajun Yang (ORCID: https://orcid.org/0000-0002-6027-3604)
- Chen Liu (ORCID: https://orcid.org/0009-0003-0430-6146)
- Jialin Li (ORCID: https://orcid.org/0000-0003-0423-2055)
- Xianjun Yu (ORCID: https://orcid.org/0000-0002-6697-7143)
- Xiaohong Tian (ORCID: https://orcid.org/0000-0003-1383-4218)
- Xiaowu Xu
- Min Zhu (ORCID: https://orcid.org/0000-0002-4800-4161)
- Miaoyan Wei
- Lichuang Men
Institutions
- Sun Yat-sen University (CN)
- American Society of Civil Engineers (US)
- Fudan University Shanghai Cancer Center (CN)
- Sun Yat-sen University Cancer Center (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-09-23
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102364
- Primary Topic
- Pancreatic and Hepatic Oncology Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00