Minimal Efficacy Observed With Eprenetapopt Plus Azacitidine in TP53-Mutant MDS

January 5, 2021
Nichole Tucker

Nichole Tucker, MA, is the Web Editor for Targeted Oncology. Tucker received her Bachelor of Arts in Mass Communications from Virginia State University and her Master of Arts in Media & International Conflict from University College Dublin.

Treatment with the combination of eprenetapopt and azacitidine did not improve complete responses in patients with TP53-mutant myelodysplastic syndromes.

Treatment with the combination of eprenetapopt (APR-246) and azacitidine (Vidaza) did not improve complete responses in patients with TP53-mutant myelodysplastic syndromes (MDS) when compared with azacitidine alone, missing the primary end point of a phase 3 clinical trial, according to a press release issued by Aprea Therapeutics, Inc.1

Results from the study showed a higher rate of complete responses of 33.3% (95% CI: 23.1% - 44.9%) compared with 22.4% (95% CI: 13.6% - 33.4%) in the azacitidine monotherapy arm, (P = .13). The difference between the 2 arms did not meet the predefined threshold for statistical significance, though.

Overall, data cutoff results show that patients do slightly better with the addition of eprenetapopt to azacitidine. Thus far, the difference is not significant. Patients who did not achieve a CR by data cutoff continue to be assessed in the study and the data will be analyzed at a later timepoint.

In terms of safety, was well-tolerated mirroring the adverse event profile observed in prior phase 2 clinical trials of either drug.

“Though we are disappointed the topline results did not reach statistical significance, we continue to believe that eprenetapopt can offer clinical benefit to patients with TP53 mutant malignancies,” said Eyal Attar, MD, chief medical officer, Aprea Therapeutics in a statement. “We will continue to analyze data as it matures and follow patients who are still receiving study treatment.”

A total of 154 patients were included in the phase 3 trial of eprenetapopt plus azacitidine and randomized 1:1 to receive either the combination or azacitidine monotherapy. Responses to therapy were measured by International Working Group 2006 (IWG 2006) criteria, which included peripheral blood counts and bone marrow blasts. The study is complete, and investigators will now analyze data on the secondary end points as the duration of patient follow-up increases.

Eprenetapopt is a small molecule which has demonstrated preclinical anti-tumor activity as treatment of multiple solid and hematologic malignancies. The agent was previously granted Breakthrough Therapy, Orphan Drug, and Fast Track designations from the FDA for the treatment of patients with MDS. Eprenetapopt was also granted Fast Track designation from the FDA for the treatment of acute myeloid leukemia (AML).

Azacitidine, an oral hypomethylating agent, has also demonstrated promise previously for the treatment of patients with de novo AML or AML secondary to prior MDS in the phase 3 QUAZAR AML-001 clinical trial (NCT01757535).2


1. Aprea Therapeutics announces results of primary endpoint from phase 3 trial of eprenetapopt in tp53 mutant myelodysplastic syndromes (MDS). News release. Aprea Therapeutics. December 28, 2020. Accessed January 5, 2020.

2. Efficacy. Onureg website. Accessed January 5, 2020.