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Expansion of trial of eprenetapopt in combination with venetoclax and azacitidine in patients with TP53-mutated AML

Jul 21, 2020

On July 16, 2020, it was announced that the phase I trial ( NCT04214860), evaluating eprenetapopt in combination with venetoclax and azacitidine in patients with TP53mutations, was expanded and will include the addition of another cohort of patients who will be treated with eprenetapopt in combination with azacitidine as a frontline treatment. The decision to expand was based upon the results from two independent phase Ib/II clinical trials ( NCT03588078and NCT03072043). 1

The lead-in safety portion of these studies demonstrated that both treatment regimens, eprenetapopt + venetoclax + azacitidine, and eprenetapopt + azacitidine, were well tolerated, and no dose-limiting toxicities were experienced. The expansion cohort will treat patients with TP53-muted AML with the triplet therapy of eprenetapopt + venetoclax + azacitidine (~ n = 30) and with the doublet therapy of eprenetapopt + azacitidine (~ n = 30) as frontline therapies. Safety and efficacy will be evaluated in both cohorts. 1

Eprenetapopt/APR-246 1

  • A small molecule that, once converted into the active form, restores wild-type p53 conformation and function, thus reactivating mutant and inactivated p53 protein to induce apoptosis in cancer cells
  • Is in clinical development for hematologic malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML)
  • Received Breakthrough Therapy, orphan drug designation, and Fast Track designation from the U.S. Food and Drug Administration (FDA) for MDS
  • Received orphan drug designation from the European Medicines Agency (EMA) for MDS, AML, and ovarian cancer
  • A pivotal phase III trial, evaluating eprenetapopt in combination with azacitidine as a frontline treatment for patients with TP53-mutated MDS, is currently ongoing

NCT04214860 2–4

  • Phase I trial of eprenetapopt in combination with venetoclax and azacitidine in TP53-mutant myeloid malignancies
  • Doses:
    • Eprenetapopt, 4.5 g/day
    • Venetoclax, 400 mg/day
    • Azacitidine, subcutaneously or intravenously, 75 mg/m 2
  • Primary outcomes: Tolerability and incidence of treatment-emergent adverse events

  1. Aprea Therapeutics. Aprea Therapeutics announces expansion of clinical trial evaluating eprenetapopt for the front-line treatment of TP53 mutant acute myeloid leukemia (AML). https://ir.aprea.com/news-releases/news-release-details/aprea-therapeutics-announces-expansion-clinical-trial-evaluating. Published Jul 16, 2020. Accessed Jul 17, 2020.
  2. Clinicaltrials.gov. APR-246 in combination with venetoclax and azacitidine in TP53-mutant myeloid malignancies. https://clinicaltrials.gov/ct2/show/NCT04214860. Updated Mar 19, 2020. Accessed Jul 17, 2020.
  3. Clinicaltrials.gov. Study of the safety and efficacy of APR-246 in combination with azacitidine. https://clinicaltrials.gov/ct2/show/NCT03588078. Updated Jan 30, 2020. Accessed Jul 17, 2020.
  4. Clinicaltrials.gov. Phase 1b/2 safety and efficacy of APR-246 w/azacitidine for tx of TP53 mutant myeloid neoplasms. https://clinicaltrials.gov/ct2/show/NCT03072043. Updated May 27, 2020. Accessed Jul 17, 2020.