Recap and Update of Positive Data from Phase Ib/II Clinical Trials of APR-246 and Azacitidine (AZA) in Patients with TP53 Mutant Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) Presented at the 2019 American Society of Hematology (ASH) An
Updated summary information on both trials can be found on the Company’s investor relations website at https://ir.aprea.com.
About the US Clinical Trial
Eligible patients in the Phase Ib/II clinical trial include HMA-naïve, TP53 mutated MDS, oligoblastic acute myeloid leukemia (AML, ≤ 30% blasts), MDS-myeloproliferative neoplasm (MDS-MPN) overlap and chronic myelomonocytic leukemia (CMML). In the Phase Ib part of the clinical trial, patients received APR-246 in a 3+3 dose escalation design (50, 75, 100 mg/kg lean body weight) IV daily over 4 days in a lead-in phase (days -14 to -10), followed by the same dose of APR-246 (days 1-4) and AZA 75 mg/m2 SC/IV daily for 7 days (days 4-10 or 4-5 and 8-12) in 28-day cycles. In the Phase II part of the clinical trial, patients receive APR-246 as a 4,500 mg fixed dose IV daily (days 1-4) and AZA daily for 7 days (days 4-10 or 4-5 and 8-12) in 28-day cycles. Primary objective in Phase Ib part of the clinical trial was safety, with AEs graded by CTCAE v4.03 and DLT assessment over 6 weeks. Secondary endpoints included response rate by IWG 2006 criteria, PFS, OS, as well as serial next generation sequencing and p53 immunohistochemistry for evaluation of clonal suppression and depth of remission. In the Phase II part of the clinical trial the primary endpoint is CR rate.
About the French Clinical Trial
Eligible patients in the Phase Ib/II clinical trial include HMA naïve, TP53 mutated MDS and acute myeloid leukemia (AML). All enrolled patients were to receive APR-246 as a 4,500 mg fixed dose IV daily (days 1-4) and AZA over 7 days (days 4-10 or 4-5 and 8-12) in 28-day cycles. The primary endpoint of the trial is CR rate.
About Myelodysplastic Syndrome
Myelodysplastic syndromes (MDS) represents a spectrum of hematopoietic stem cell malignancies in which bone marrow fails to produce sufficient numbers of healthy blood cells. Approximately 30-40% of MDS patients progress to acute myeloid leukemia (AML) and mutation of the p53 tumor suppressor protein is thought to contribute to disease progression. Mutations in p53 are found in up to 20% of MDS and AML patients and are associated with poor overall prognosis.
About p53 and APR-246
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.
APR-246 is a small molecule that has demonstrated reactivation of mutant and inactivated p53 protein – by restoring wild-type p53 conformation and function – and thereby induce programmed cell death in human cancer cells. Pre-clinical anti-tumor activity has been observed with APR-246 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 I/II clinical program with APR-246 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 APR-246 and azacitidine for frontline treatment of TP53 mutant MDS is ongoing. APR-246 has received Orphan Drug and Fast Track designations from the
The Company may use, and intends to use, its investor relations website at https://ir.aprea.com as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD.
Certain information contained in this press release includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our clinical trials and regulatory submissions. We may, in some cases use terms such as “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team that involve risks, potential changes in circumstances, assumptions, and uncertainties. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including risks related to the success and timing of our clinical trials or other studies and the other risks set forth in our filings with the
Christian S. SchadePresident and Chief Executive Officer firstname.lastname@example.org Gregory A. KorbelVice President of Business Development email@example.com
Source: Aprea Therapeutics