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

NCT03386526 | Completed Phase 1 FDA Drug

• 1 other identifier: APG-1387-US-001
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Advanced Solid Tumors or Hematologic Malignancies

Keywords

IAP inhibitor

Outcome Measures

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

  18-24 months

Secondary Outcomes (5)

• Anti-tumor effects of APG-1387 as a single agent

  18-24 months

• Pharmacokinetic evaluation

  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

  18-24 months

• Preliminary biomarker assessment

  18-24 months

• Pharmacokinetic evaluation

  18-24 months

Study Arms (1)

APG-1387 for Injection

EXPERIMENTAL

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

APG-1387 for Injection DRUG

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

APG-1387 for Injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed solid tumor or hematological malignancies
• Life expectancy ≥ 3 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• Corrected QT interval (QTc) ≤ 450 ms in males, and ≤ 470 ms in females
• Adequate hematologic function
• International normalized ratio (INR), prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5 x upper limit of normal (ULN)
• Adequate renal and liver function
• Willingness to use contraception
• Ability to understand and willingness to sign a written informed consent form
• Willingness and ability to comply with study procedures and follow-up examination
• Have provided tissue for biomarker analysis from a newly or recently-obtained biopsy of a tumor lesion not previously irradiated

You may not qualify if:

• Received chemotherapy within 21 days (42 days for nitrosoureas or mitomycin C) prior to entering the study
• Received hormonal, biologic (\< 2 half-lives), small molecule targeted therapies or other anti-cancer therapy within 21 days of study entry
• Radiation or surgery within 14 days of study entry, thoracic radiation within 28 days of study entry
• 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
• Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to ≤ Grade 1 except alopecia
• Requirement for corticosteroid treatment, with the exception of megestrol, local use of steroid
• Use of therapeutic anticoagulants
• International normalized ratio (INR) or activated partial thromboplastin time (APTT) ≥ 1.5 x ULN
• Concurrent treatment with an investigational agent or device within 28 days prior to the first dose of therapy
• Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry
• Neurologic instability per clinical evaluation due to tumor involvement of the central nervous system (CNS)
• History of Bell's palsy
• Active rheumatoid arthritis (RA), active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation
• Active infection requiring systemic antibiotic/ antifungal medication
• Known or suspected Wilson's Disease

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (3)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

START Midwest

Grand Rapids, Michigan, 49503, United States

Location

The START Center for Cancer Care

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• 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.

  PMID: 38790057 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

APG-1387; Injections

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Yifan Zhai, MD, PhD

  Ascentage Pharma Group Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: December 29, 2017
• Study Start: November 21, 2017
• Primary Completion: October 31, 2022
• Study Completion: November 30, 2022
• Last Updated: February 1, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)