TP53,   General AML

An open-label phase I dose-finding study of APR-246 in hematological malignancies

TP53 mutations are common in relapsed/refractory (R/R) disease and confer a dismal prognosis in hematological malignancies. APR-246 is the first compound targeting mutant p53 to be used in a clinical trial. Eight patients with R/R non-M3 Acute Myeloid Leukemia (AML) were included in the trial. S. Deneberg, et al., published their results in Blood Cancer Journal in July 2016. The trial was conducted in accordance to the Declaration of Helsinki and ICH-GCP guidelines and was registered at (NCT00900614).

The key findings were:
  • One AML patient (67.5mg/kg dose) showed a >25% reduction of blast cell count in their peripheral blood. However, the patient was not given any additional treatment due to experiencing serious adverse events (judged as unrelated to the study treatment) at the end of the follow-up period.
  • A previously stem cell-transplanted patient with AML (03-101) in third relapse was treated with 135mg/kg APR-246 and went into complete remission. A month prior to inclusion, the patient had 83% blasts in their peripheral blood (judged as overt relapse and no bone marrow was taken) compared with 4% after 4 days of APR-246 treatment and 0% at day 21 bone marrow examination.

These data provide a basis for the further exploration of the use of APR-246 in hematological indications, preferentially in combination with standard chemotherapy.

  1. Deneberg S, et al. An open-label phase I dose-finding study of APR-246 in hematological malignancies. Blood Cancer J. 2016 Jul 15; 6(7): e447. DOI: 10.1038/bcj.2016.60.
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