A Phase I Study of APR-246 with Venetoclax and Azacitidine in People with Acute Myeloid Leukemia


Full Title

Phase I Study of APR-246 in Combination with Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies


This study has two parts. One part will be for patients with acute myeloid leukemia (AML) who have alterations in a protein called TP53. In these patients, researchers want to find the highest dose of the investigational drug APR-246 that can be given safely with venetoclax, or with venetoclax and azacitidine. This first part of the study is called the “dose-finding” part. Once researchers have found the highest dose of APR-246 that can be given safely, that dose will be assessed in the second (“expansion”) part of the study.

The expansion part of the study will treat mostly patients with AML who have TP53 mutations, but will also include some patients with myelodysplastic syndromes (MDS) who have TP53 mutations. Patients will receive either APR-246 and venetoclax, or APR-246 plus venetoclax and azacitidine. The purpose of the expansion part of the study is to make sure that the dose of APR-246 found during the dose-finding part is still safe in more patients. The expansion part will also look for signs that this combination of treatments might be effective for treating patients with AML and MDS with TP53 mutations.

APR-246 is designed to inhibit cancer growth by targeting mutated TP53 proteins. It is given intravenously (by vein). Azacitidine is a standard therapy for blood cancers and is given intravenously or by subcutaneous (under the skin) injection. Venetoclax blocks Bcl-2, a protein in cancer cells that helps them survive and resist the effects of cancer treatments. By blocking Bcl-2, venetoclax may kill cancer cells and/or make them more vulnerable to the effects of other therapies. It is taken orally (by mouth).


To be eligible for this study, patients must meet several criteria, including but not limited to the following:

  • Patients in the dose-finding part of the study must have AML that contains mutated TP53 and continues to grow despite prior therapy with azacitidine or decitabine, or have AML that contains mutated TP53 and has never been treated.
  • Patients in the expansion part of the study must have previously treated AML or MDS with TP53 mutations, or previously untreated AML with TP53 mutations.
  • Patients must be able to walk and do routine activities for more than half of their normal waking hours.
  • This study is for patients age 18 and older.

For more information about this study and to inquire about eligibility, please contact Dr. Aaron Goldberg at 212-639-2126.





Disease Status

Relapsed or Refractory