APG-2575 for treating blood cancers

A Phase I Study of Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Property of Orally Administered APG-2575 in Patients With Hematologic Malignancies

This study is testing a new oral medication called APG-2575 to see if it can safely help people with certain blood cancers who haven't had success with other treatments.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ascentage Pharma Group Inc. (industry)
• Drugs / interventions: chemotherapy, Radiation
• Locations: 5 sites (Jacksonville, Florida and 4 other locations)
• Trial ID: NCT03537482 on ClinicalTrials.gov

What this trial studies

This is a multi-center, open-label Phase I study evaluating the safety and tolerability of APG-2575, an oral medication administered daily for four weeks. The study includes a dose escalation phase where the initial dose of 20 mg may be increased to higher levels based on patient response and safety observations. Patients with various B-cell hematologic malignancies who have not responded to previous treatments will be enrolled. The study aims to determine the maximum tolerated dose (MTD) of APG-2575 and assess its pharmacokinetics and pharmacodynamics.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with relapsed or refractory B-cell hematologic malignancies.

Not a fit: Patients who have not been diagnosed with hematologic malignancies or those who are not relapsed or refractory to previous treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat blood cancers.

How similar studies have performed: Other studies have shown promise with similar approaches in targeting hematologic malignancies, but the specific use of APG-2575 is novel.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years old.
2. Histologically confirmed diagnosis of either one of the B-cell hematologic malignancies including multiple myeloma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, and non-Hodgkin's lymphoma such as mantle cell lymphoma, diffuse large B cell lymphoma, Waldenstrom macroglobulinemia (WM) and acute myeloid leukemia
3. Patient must have relapsed or refractory to, intolerant to, or are considered ineligible for therapies known to provide clinical benefit. In addition,

   a. AML Patients will be eligible if they have failed standard induction regimen, are not considered candidate for further chemotherapy or stem cell transplantation or have primary refractory AML.
4. Life expectancy ≥ 3 months.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1 in dose escalation ; 0-2 in dose expansion.
6. QTc interval ≤450ms in males, and ≤470ms in females.
7. Adequate bone marrow function independent of growth factor:
8. Absolute neutrophil count (ANC) ≥1.0 X 109/L.
9. Hemoglobin ≥ 8.0 g/dL.
10. Platelets count ≥ 30 X 109/L (entry platelet count must be independent of transfusion within 7 days of first dose).
11. Adequate renal and liver function as indicated by:

Exclusion Criteria:

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

1. Prior history of allogeneic cell transplant.
2. Subjects have been diagnosed with Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukemia.
3. Received chemotherapy within 14 days (42 days for nitrosoureas or mitomycin C) prior to entering the study.
4. Received biologic (\< 28 days), small molecule targeted therapies (\< 5 half-life) or other anti-cancer therapy within 21 days of study entry.
5. Radiation within 14 days of study entry, thoracic radiation within 28 days of study entry.
6. Has gastrointestinal conditions that could affect the absorption of APG-2575 in the opinion of the Investigator.
7. Has known active central nervous system (CNS) involvement.
8. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to ≤ Grade 1 except alopecia or neuropathy.
9. Concurrent treatment with an investigational agent, 14 days for small molecular agents and/or 28 days for biologics treatment prior to the first dose of therapy.
10. Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patients with active wound healing, patients who have had major surgery within 28 days from study entry, and patients who have had minor surgery within 14 days of study entry.
11. Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry.
12. Active rheumatoid arthritis (RA), active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation.
13. Active infection requiring systemic antibiotic/ antifungal medication, known clinically active hepatitis B or C infection, or on antiretroviral therapy for HIV disease.

Where this trial is running

Jacksonville, Florida and 4 other locations

• Mayo Clinic — Jacksonville, Florida, United States (RECRUITING)
• Duke Unviersity — Durham, North Carolina, United States (COMPLETED)
• MDACC — Houston, Texas, United States (RECRUITING)
• St. Vincent Hospital — Fitzroy, Victoria, Australia (RECRUITING)
• Epworth Healthcare — Richmond, Victoria, Australia (RECRUITING)

Study contacts

• Study coordinator: Laura Glass

Conditions: Hematologic Malignancies