Aprea Therapeutics Announces Results of Primary Endpoint from Phase 3 Trial of Eprenetapopt in TP53 Mutant Myelodysplastic Syndromes (MDS)
- The trial failed to meet its primary endpoint of complete remission (CR) rate
- CR rate was 53% higher in eprenetapopt with AZA arm compared to AZA alone, but did not reach statistical significance
While analysis of certain secondary endpoints (ORR and duration of responses) appears to favor the experimental arm at this data cut, they are not significantly different. The median duration of overall survival at the primary data cut was similar between the arms. Additional patients in the study who have not achieved a CR remain on study treatment and the data will be analyzed at future pre-specified timepoints as set forth in the statistical analysis plan. The combination of eprenetapopt with AZA appeared well-tolerated, with an adverse event profile that was similar to the Company’s prior Phase 2 clinical trials. Subsequent analyses of the trial data, including secondary endpoints, will be conducted as the duration of patient follow-up increases. The Company expects to present the data at a future scientific conference.
“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 Dr.
About the Phase 3 Trial in TP53 Mutant MDS
The Phase 3 trial enrolled 154 TP53 mutant MDS patients, randomized 1:1 to either the eprenetapopt with AZA arm or the AZA alone arm. Response criteria are those defined by
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About p53, eprenetapopt and APR-548
The p53 tumor suppressor gene is the most frequently mutated gene in human cancer, occurring in approximately 50% of all human tumors. These mutations are often associated with resistance to anti-cancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer.
Eprenetapopt (APR-246) is a small molecule that has demonstrated reactivation of mutant and inactivated p53 protein – by restoring wild-type p53 conformation and function – thereby inducing programmed cell death in human cancer cells. Pre-clinical anti-tumor activity has been observed with eprenetapopt in a wide variety of solid and hematological cancers, including MDS, AML, and ovarian cancer, among others. Additionally, strong synergy has been seen with both traditional anti-cancer agents, such as chemotherapy, as well as newer mechanism-based anti-cancer drugs and immuno-oncology checkpoint inhibitors. In addition to pre-clinical testing, a Phase 1/2 clinical program with eprenetapopt has been completed, demonstrating a favorable safety profile and both biological and confirmed clinical responses in hematological malignancies and solid tumors with mutations in the TP53 gene.
A pivotal Phase 3 clinical trial of eprenetapopt and azacitidine for frontline treatment of TP53 mutant MDS has been completed and additional clinical trials in hematologic malignancies and solid tumors are ongoing. Eprenetapopt has received Breakthrough Therapy, Orphan Drug and Fast Track designations from the FDA for MDS, Fast Track designation from the FDA for AML, and Orphan Drug designation from the
APR-548 is a next-generation small molecule p53 reactivator. APR-548 has demonstrated high oral bioavailability, enhanced potency relative to eprenetapopt in TP53 mutant cancer cell lines and has demonstrated in vivo tumor growth inhibition following oral dosing of tumor-bearing mice. Enrollment in a Phase 1 clinical trial of APR-548 is anticipated to begin in the first quarter of 2021.
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Source: Aprea Therapeutics