Eprenetapopt (APR-246) is a p53 reactivator being investigated in several TP53-mutated hematologic malignancies. It has received Breakthrough Therapy, orphan drug, and Fast Track designations from the U.S Food and Drug Administration for TP53-mutated myelodysplastic syndromes (MDS).
The phase III trial NCT03745716 explores the combination of eprenetapopt with azacytidine versus azacytidine alone for untreated patients with at least one TP53 mutation, which is not benign or likely benign. On December 28, 2020, the trial sponsor announced that the trial had not met its primary endpoint: the complete response (CR) rates in the combination arm were superior but not statistically significant.
At data cut-off (N = 154), 33.3% (95% CI, 23.1%–44.9%) of patients receiving eprenetapopt with azacytidine achieved a CR, while in control arm the CR rate was 22.4% (95% CI, 13.6%–33.4%, p = 0.13). However, the press release states that with longer follow-up, secondary endpoints such as overall response rate and duration of response might favor the combination arm.
The safety profile of eprenetapopt plus azacytidine is consistent to date with previously reported single-arm phase II studies, like the GFM-APR246 trial (NCT03588078), presented at the 25th Congress of the European Hematology Association (EHA) by Thomas Cluzeau. Watch below a summary of their results.