NEW YORK – Suzhou, China-headquartered Ascentage Pharma said on Tuesday that regulators in China have given it permission to start a Phase IIa trial of the MDM2-p53 inhibitor, dubbed APG-115, for the treatment of relapsed or refractory T-cell prolymphocytic leukemia.
T-PLL is a rare and aggressive leukemia characterized by a mutation in ATM located in the 11q22-23 region in the vast majority of cases. Patients with this disease tend not to respond to available chemotherapies and to live between six and nine months on average after diagnosis.
The global, multicenter trial will explore the safety, pharmacokinetics, and preliminary efficacy of APG-115 as a monotherapy or in combination with APG-2575, a BCL-2-selective inhibitor also being developed by Ascentage, in relapsed or refractory T-PLL.
"Combination therapy is playing an increasingly important role in cancer treatment. Concurrent inhibition of both MDM2-TP53 and BCL-2 apoptosis pathways by the combination of APG-115 and APG-2575 has great therapeutic potential in triggering 'synthetic lethality' and effectively induce cell death by simultaneously blocking two important nodes of both apoptosis pathways," Ascentage Chief Medical Officer Yifan Zhai said in a statement, adding that the combination of the two oral targeted drugs may offer a chemotherapy-free option for T-PLL patients.
APG-115 is designed to bind to MDM2 and block it from interacting with p53, which in turn allows p53 to suppress tumors. In xenograft models of acute myeloid leukemia and mantle cell lymphoma, the drug has produced a 100 percent response rate. APG-115 is currently being investigated in multiple studies for solid and hematologic cancers in China and in the US, and the study in T-PLL involving this drug has also received permission to begin from the US Food and Drug Administration.