Clinical Path

A Phase I dose-escalation safety study of APR-246 monotherapy in patients with refractory hematological malignancies or prostate cancer was conducted to establish the safety, tolerability and highest feasible dose of APR-246. In addition to the Phase I study, clinical trials in p53-mutated high-grade serous ovarian cancer (HGSOC) have been conducted, and have collectively established safe dosing and generated encouraging signals of efficacy. Hematologic malignancies are the focus of ongoing and future clinical development for Aprea’s p53 reactivators. A Phase III clinical trial, as well as Phase II clinical trials, of APR-246 in combination with azacitidine for the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are underway.


Myelodysplastic syndromes (MDS) represents a spectrum of hematopoietic stem cell malignancies in which bone marrow fails to produce sufficient numbers of healthy blood cells. Approximately 30-40% of MDS patients progress to acute myeloid leukemia (AML) and mutation of the p53 tumor suppressor protein is thought to contribute to disease progression. Mutations in p53 are found in up to 20% of de novo MDS and AML patients and are associated with poor overall prognosis.

Emerging data from ongoing Phase Ib/II clinical trials of APR-246 in combination with azacitidine for the treatment of p53-mutated, high-risk MDS and AML continue to provide evidence in support of the safety, tolerability and efficacy of APR-246. Preliminary results have been presented at the 2018 American Association for Cancer Research annual meeting, the 2018 European Hematology Association annual meeting, and the 2018 American Society of Hematology annual meeting. Based on the high overall response rate (ORR) and complete response rate (CR) in these studies, a Phase III study in p53-mutated, high-risk MDS patients has been initiated. Additional studies in MDS and AML, as well as other hematologic malignancies, are planned.