Sponsor decision

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

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).

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 was terminated.

28 days