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

Shi, Si; Zhang, Jian; Liu, Rujiao; Gao, Shuiping; Xu, Jin; Wang, Wei; Wei, Miaoyan; Li, Jialin et al. · Cell Rep Med · 2025

case_series · Level IV

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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/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).

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