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

Overview

APG-1387 is a potent, bivalent small-molecule 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 2 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.

SparkCures ID 1035
Trial Phase Phase 1/2
Enrollment 90 Patients
Treatments
Trial Sponsors
  • Ascentage Pharma Group Inc.
NCT Identifier

NCT03386526

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

Inclusion Criteria:

  1. Histologically or cytologically confirmed solid tumor or hematological malignancies
  2. Life expectancy ≥ 3 months
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
  4. QTc interval ≤ 450 ms in males, and ≤ 470 ms in females
  5. Adequate hematologic function
  6. International normalized Ratio (INR), Prothrombin Time (PT) or Activated Partial Thromboplastin time (aPTT) ≤1.5 X ULN
  7. Adequate renal and liver function
  8. Willingness to use contraception
  9. Ability to understand and willingness to sign a written informed consent form
  10. Willingness and ability to comply with study procedures and follow-up examination
  11. Have provided tissue for biomarker analysis from a newly or recently-obtained biopsy of a tumor lesion not previously irradiated

Exclusion Criteria:

Patients who meet any of the following exclusion criteria are not to be enrolled in this study.

  1. Received chemotherapy within 21 days (42 days for nitrosoureas or mitomycin C) prior to entering the study
  2. Received hormonal, biologic (< 2 half-lives), small molecule targeted therapies or other anti-cancer therapy within 21 days of study entry
  3. Radiation or surgery within 14 days of study entry, thoracic radiation within 28 days of study entry.
  4. Has known active central nervous (CNS) metastases and/or carcinomatous meningitis. Patients who have received prior radiotherapy for previous brain metastasis must have discontinued steroids for 14 days prior to study entry and be clinically stable.
  5. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to ≤ Grade 1 except alopecia
  6. Requirement for corticosteroid treatment, with the exception of megestrol, local use of steroid.
  7. Use of therapeutic anticoagulants
  8. International normalized ratio (INR) or activated partial thromboplastin time (APTT) ≥ 1.5 x ULN
  9. Concurrent treatment with an investigational agent or device within 28 days prior to the first dose of therapy
  10. Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry
  11. Neurologic instability per clinical evaluation due to tumor involvement of the central nervous system (CNS).
  12. History of Bell's palsy
  13. Active rheumatoid arthritis (RA), active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation
  14. Active infection requiring systemic antibiotic/ antifungal medication,
  15. Known or suspected Wilson's Disease.
  16. Prior treatment with IAP inhibitors
  17. History of hypersensitivity to paclitaxel, or any therapeutic antibody
  18. Has an active autoimmune disease, or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
  19. Is on chronic systemic steroid therapy
  20. Has received a live vaccine within 30 days prior to first dose.
  21. Has had an allogeneic tissue/solid organ transplant, prior stem cell or bone marrow transplant

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

South Texas Accelerated Research Therapeutics (START)

San Antonio, TX

Texas
South Texas Accelerated Research Therapeutics (START)

San Antonio, TX

Resources

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