APG-1387 in Patients With Advanced Solid Tumors or Hematologic Malignancies

Summary

APG-1387 is a potent, bivalent small-molecule Inhibitor of Apoptosis Protein (IAP) antagonist. APG-1387 has shown strong dose- and schedule-dependent antitumor activities in multiple human cancer xenograft models, APG-1387 also demonstrates its synergistic effect in combination with immune checkpoint inhibitor anti-PD-1 antibody, and such a combinatory effect was further enhanced by chemotherapeutic agent. A total of 35 patients with advanced solid tumors or lymphomas have been treated with APG-1387 in two Phase I dose-escalation studies in Australia and in China. Ten dose levels have been tested ranging from 0.3 mg to 45 mg in these two studies. Based on the preliminary results, APG-1387 is well-tolerated at the dose levels evaluated to date. APG-1387 is intended for the treatment of patients with advanced solid tumors and hematologic malignancies. After establishing the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and/or recommended phase 2 dose (RP2D), several Ib /II studies will be implemented accordingly to further access the antitumor effects of APG-1387 in combination with either pembrolizumab or the chemotherapeutic agents.

Timeline

Start

2017-11-21

Primary completion

2022-10-31

Completion

2022-11-30

Publications

• Pan W, Luo Q, Liang E, Shi M, Sun J, Shen H, Lu Z, Zhang L, Yan X, Yuan L, Zhou S, Yi H, Zhai Y, Qiu MZ, Yang D. Synergistic effects of Smac mimetic APG-1387 with anti-PD-1 antibody are attributed to increased CD3 + NK1.1 + cell recruitment secondary to induction of cytokines from tumor cells. Cancer Cell Int. 2024 May 24;24(1):181. doi: 10.1186/s12935-024-03373-7.

Drugs

Indications