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

Phase 1 Study to Evaluate Safety and Efficacy of APR-548 in Combination With Azacitidine for the Treatment of TP53-Mutant Myelodysplastic Syndromes

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

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndromes; MDS
• Intervention / Treatment: Drug: APR-548 + Azacitidine

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).

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institue
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Dose level 1	Drug: APR-548 + Azacitidine; APR-548 monotherapy period followed by APR-548 in combination with Azacitidine
Experimental: Cohort 2; Dose level 2	Drug: APR-548 + Azacitidine; APR-548 monotherapy period followed by APR-548 in combination with Azacitidine
Experimental: Cohort 3; Dose level 3	Drug: APR-548 + Azacitidine; APR-548 monotherapy period followed by APR-548 in combination with Azacitidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Investigate the "Number of Participants With Treatment Emergent Adverse Events From Treatment With APR-548 as Monotherapy and in Combination With Azacitidine	Occurrence of frequency of treatment emergent adverse events by reviewing safety data including AEs, vital signs, laboratory data, ECG, ophthalmologic assessment findings, and other physical exam findings.	Through study completion, approximately 28 days

Collaborators and Investigators

• Sponsor: Aprea Therapeutics
• Investigators: Study Director: Joachim Gullbo, MD, Theradex Oncology

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2021
• Primary Completion (Actual): April 25, 2022
• Study Completion (Actual): April 25, 2022

Study Registration Dates

• First Submitted: November 13, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Syndrome; Preleukemia; Myelodysplastic Syndromes; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Azacitidine
• Other Study ID Numbers: A20-11202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No