A Phase 1 interventional study of APG-1387 for Injection in Advanced Solid Tumors or Hematologic Malignancies, sponsored by Ascentage Pharma Group Inc.. Completed at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-02-01.
Sponsored by Ascentage Pharma Group Inc. · Phase 1, Interventional, and Treatment
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.
Exclusion Criteria:
APG-1387 will be explored sequentially using a standard 3+3 escalation scheme at the dose escalation phase and up to 20 patient per group at the dose expansion phase.
Drug: APG-1387 for Injection
Multiple dose cohorts, 30 minute IV infusion, once weekly for 3 weeks of a 21-day cycle
Maximum Tolerated Dose (MTD)
Patients with APG-1387 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.03
Time frame: 18-24 months
Anti-tumor effects of APG-1387 as a single agent
Response will be evaluated every 2 cycles (8 weeks), according to the revised RECIST Guideline, Version 1.1 or the Revised Response Criteria for Malignant Lymphoma
Time frame: 18-24 months
Pharmacokinetic evaluation
Maximum plasma concentration (Cmax) will be assessed in the patients treated with APG-1387
Time frame: 18-24 months
Anti-tumor effects of APG-1387 in combination with pembrolizumab or combination with paclitaxel and carboplatin in patients with advanced solid tumors
Response will be evaluated every 2 cycles (8 weeks), according to the revised RECIST Guideline, Version 1.1 or the Revised Response Criteria for Malignant Lymphoma
Time frame: 18-24 months
Preliminary biomarker assessment
Tumor biopsy and peripheral blood sample at baseline and 15-21 days after administration of APG-1387 alone or in combination with systemic anti-cancer therapy
Time frame: 18-24 months
Pharmacokinetic evaluation
Area under the plasma concentration versus time curve (AUC) of APG-1387 will be assessed on patients treated with APG-1387
Time frame: 18-24 months
Plan to share: No
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Ascentage Pharma Group Inc.