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CompletedNCT03386526Updated Feb 1, 2023

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

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

Phase
Phase 1
Study type
Interventional
Enrollment
90
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Advanced Solid Tumors or Hematologic Malignancies

Keywords

  • IAP inhibitor
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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. Corrected QT interval (QTc) ≤ 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 upper limit of normal (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

Exclusion Criteria:

  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
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
90 participants (actual)

Study arms

  • 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

Interventions

  • DrugAPG-1387 for Injection

    Multiple dose cohorts, 30 minute IV infusion, once weekly for 3 weeks of a 21-day cycle

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. Pharmacokinetic evaluation

    Maximum plasma concentration (Cmax) will be assessed in the patients treated with APG-1387

    Time frame: 18-24 months

  3. 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

  4. 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

  5. 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

06

Study locations

3 sites
  • University of Michigan
    Ann Arbor, Michigan 48109, United States
  • START Midwest
    Grand Rapids, Michigan 49503, United States
  • The START Center for Cancer Care
    San Antonio, Texas 78229, United States
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03386526
Lead sponsor
Ascentage Pharma Group Inc.
Responsible party
Sponsor
First posted
Dec 29, 2017
Start date
Nov 21, 2017
Primary completion
Oct 31, 2022
Completion
Nov 30, 2022
Last update
Feb 1, 2023

Study contacts

Yifan Zhai, MD, PhD
study chair · Ascentage Pharma Group Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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