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

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ClinicalTrials.gov Identifier: NCT03386526
Recruitment Status : Recruiting
First Posted : December 29, 2017
Last Update Posted : December 29, 2017
Sponsor:
Information provided by (Responsible Party):
Ascentage Pharma Group Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors or Hematologic Malignancies Drug: APG-1387 for Injection Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of APG-1387 as A Single Agent or in Combination With Systemic Anti-Cancer Agents in Patients With Advanced Solid Tumors or Hematologic Malignancies
Actual Study Start Date : December 12, 2017
Estimated Primary Completion Date : June 11, 2019
Estimated Study Completion Date : December 11, 2019

Arm Intervention/treatment
Experimental: APG-1387 for Injection
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



Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 18-24 months ]
    Patients with APG-1387 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.0


Secondary Outcome Measures :
  1. Anti-tumor effects of APG-1387 as a single agent [ Time Frame: 18-24 months ]
    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 (Cheson, 2007).

  2. Pharmacokinetic evaluation [ Time Frame: 18-24 months ]
    Maximum plasma concentration (Cmax) will be assessed in the patients treated with APH-1387

  3. Anti-tumor effects of APG-1387 in combination with pembrolizumab , or combination with paclitaxel and carboplatin in patients with advanced solid tumors [ Time Frame: 18-24 months ]
    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 (Cheson, 2007).

  4. Preliminary biomarker assessment [ Time Frame: 18-24 months ]
    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

  5. Pharmacokinetic evaluation [ Time Frame: 18-24 months ]
    Area under the plasma concentration versus time curve (AUC) of APG-1387 will be assessed on patients treated with APG-1387



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03386526


Contacts
Contact: Isabel Jimenez, RN, MSN (210) 593-5265 Isabel.Jimenez@startsa.com

Locations
United States, Texas
South Texas Accelerated Research Therapeutics, LLC Recruiting
San Antonio, Texas, United States, 78229
Contact: Isabel Jimenez, RN, MSN    210-593-5265    Isabel.Jimenez@startsa.com   
Principal Investigator: Drew Resco, M.D.         
Sponsors and Collaborators
Ascentage Pharma Group Inc.
Investigators
Study Director: Yifan Zhai, M.D., Ph.D. Ascentage Pharma Group Inc.

Responsible Party: Ascentage Pharma Group Inc.
ClinicalTrials.gov Identifier: NCT03386526     History of Changes
Other Study ID Numbers: APG-1387-US-001
First Posted: December 29, 2017    Key Record Dates
Last Update Posted: December 29, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ascentage Pharma Group Inc.:
IAP inhibitor

Additional relevant MeSH terms:
Neoplasms