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APR-548 in Combination With Azacitidine for the Treatment of TP53 Myelodysplastic Syndromes (MDS)

Phase 1
Terminated
Conditions
MDS
Myelodysplastic Syndromes
Interventions
Registration Number
NCT04638309
Lead Sponsor
Aprea Therapeutics
Brief Summary

Phase 1 study evaluating the safety and efficacy of APR-548 in combination with Azacitidine for the treatment of TP53-Mutant Myelodysplastic Syndromes.

Detailed Description

Open-label first-in-human (FIH) phase 1 clinical trial assessing the safety, pharmacokinetics (PK), and clinical activity of orally (p.o.) administered APR-548 alone and in combination with azacitidine for the treatment of TP53-mutant myelodysplastic syndromes (MDS).

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
4
Inclusion Criteria
  1. Provision of signed and dated, written informed consent prior to any study specific procedures.

  2. Documented diagnosis of TP53-mutant MDS, according to WHO criteria that is relapsed/refractory or previously untreated MDS.

  3. Adequate organ function as defined by the following laboratory values:

    1. Creatinine clearance ≥60 mL/min (by Cockcroft-Gault method, Appendix I),
    2. Total serum bilirubin ≤1.5 × upper limit of normal (ULN) unless due to Gilbert's syndrome or MDS organ involvement,
    3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN, unless due to MDS organ involvement.
  4. Age ≥18 years at the time of signing the informed consent form.

  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix II).

  6. Projected life expectancy of ≥12 weeks.

  7. Clear ocular media and adequate pupil dilation to permit fundus examination and retinal imaging.

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Exclusion Criteria
  1. Cardiac abnormalities, which includes, but not limited to:

    1. Myocardial infarction within six months prior to enrollment
    2. New York Heart Association Class III or IV heart failure or known LVEF <40%
  2. Concomitant malignancies or previous malignancies with less than a 1 year disease-free interval at the time of signing informed consent.

  3. Use of cytotoxic chemotherapeutic agents, or experimental agents for the treatment of MDS within 14 days or 5 half-lives of the product (whichever is shorter) of the first day of study drug treatment.

  4. Prior exposure to eprenetapopt (APR-246).

  5. A female subject who is pregnant or breast-feeding.

  6. Known history of human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection.

  7. Malabsorption syndrome or other condition likely to affect gastrointestinal absorption of APR-548.

  8. Known history or current evidence of ocular disease in either eye

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Cohort 2APR-548 + AzacitidineDose level 2
Cohort 1APR-548 + AzacitidineDose level 1
Cohort 3APR-548 + AzacitidineDose level 3
Primary Outcome Measures
NameTimeMethod
To investigate the safety and tolerability of APR-548 as monotherapy and in combination with azacitidine.Through study completion, approximately 1 year

Occurence of dose limiting toxicities (DLTs) and frequency of treatment emergent and serious adverse events.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (4)

Dana Farber Cancer Institue

🇺🇸

Boston, Massachusetts, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

H. Lee Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

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