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Rebecca Olin, MD, MS


Eprenetapopt Plus Azacitidine Under Study in TP53-Mutant AML

By: Anna Nowogrodzki
Posted: Thursday, February 11, 2021

Intravenous eprenetapopt in combination with azacitidine yielded an overall response rate of 71% in patients with TP53-mutant myelodysplastic syndrome or acute myeloid leukemia (AML), according to a recent study. David A. Sallman, MD, of Moffitt Cancer Center, Tampa, Florida, and colleagues published their results in the Journal of Clinical Oncology. Eprenetapopt (APR-246) is a novel, first-in-class, small molecule that restores wild-type p53 functions in TP53-mutant cells.

“The data are promising and support the current phase III, multicenter trial,” Dr. Sallman said in a Moffitt press release. “There is clearly a need for new targeted therapies for this patient population.”

The phase Ib/II study included 55 patients with TP53-mutant myelodysplastic syndrome or AML. A total of 11 patients had AML; 40 had myelodysplastic syndrome, and 4 had myelodysplastic syndrome/myeloproliferative neoplasms. Patients received azacitidine intravenously or subcutaneously, plus an infusion of eprenetapopt. The dose-escalation phase included 12 patients who received varying doses of eprenetapopt plus azacitidine. No dose-limiting toxicities occurred. In phase II, patients received 100 mg/kg lean body mass/day of eprenetapopt plus azacitidine.

The overall response rate was 71%, and 44% of patients achieved a complete response. Among patients with AML, the overall response rate was 64%, and the complete response rate was 36%. Among patients with myelodysplastic syndrome, the rates were somewhat higher, with an overall response rate of 73% and a complete response rate of 50%. Responding patients had significantly better overall survival (14.6 months) than nonresponding patients (7.5 months).

Adverse events were similar to reported adverse events for the two drugs alone. The most common grade 3 or higher adverse events were febrile neutropenia (33%), leukopenia (29%), neutropenia (29%), thrombocytopenia (25%), and lung infection (25%). However, less than 5% of grade 3 or higher adverse events were considered potentially related to eprenetapopt treatment. No treatment-related deaths were reported.

Disclosure: For full disclosures of the study authors’, visit

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