FDA grants APG-115 orphan drug designation for the treatment of AML and MDS

On October 9, 2020, the U.S. Food and Drug Administration (FDA) granted APG-115 orphan drug designation for the treatment of acute myeloid leukemia (AML). APG-115 is an orally available, selective, small molecule inhibitor of MDM2 (an E3 ubiquitin-protein ligase), which works by blocking the MDM2-p53 interaction, thus activating the tumor suppressor activity of p53.¹ In September 2020, this drug also received FDA orphan drug designation for the treatment of gastric cancer.²

APG-115 is the first MDM2-p53 inhibitor to enter clinical studies in China and is currently also being tested in the U.S. for the treatment of solid tumors. A phase Ib study (NCT04275518), investigating APG-115 as a single agent or in combination with cytarabine or azacitidine for patients with relapsed/refractory (R/R) AML or myelodysplastic syndromes (MDS), is currently recruiting in China.^1,2

NCT04275518 study design²

• An open label, phase Ib study to investigate the pharmacokinetics and pharmacodynamics of APG-115 in adult patients with R/R AML, or relapsed/progressed, high/very high-risk MDS.
• Three-stage study:
  1. 3+3 dose escalation to determine dose-limiting toxicities and maximum tolerated dose of APG-115 as a single agent given orally, once daily from Days 1–7, every 28 days.
  2. 3+3 dose escalation to determine the dose-limiting toxicities and maximum tolerated dose of: APG-115 plus cytarabine 1mg/m² intravenously, once daily, on Days 3–7 every 28 days in the AML cohort; or APG-115 plus azacytidine 75 mg/m² subcutaneously, twice daily, on Days 1–7 every 28 days in the MDS cohort.
  3. Dose expansion of the combination regimens.

• Secondary endpoints: Overall response rate and overall survival.
• Estimated enrollment: 90 patients.

This second FDA orphan drug designation for APG-115 is hoped to accelerate global clinical development and commercialization and allow for more patients to benefit as soon as possible.