Suzhou-based Ascentage Pharma (HKG: 6855) announced the latest clinical development of its olverembatinib (HQP1351), a third-generation BCR-ABL-targeted tyrosine kinase inhibitor (TKI), Bcl-2 inhibitor lisaftoclax (APG-2575), and MDM2-p53 inhibitor alrizomadlin (APG115) at the 64th American Society of Hematology (ASH) annual meeting this year.
Olverembatinib in CML and Ph+ALL
Olverembatinib can overcome drug resistance to Ponatinib in patients with advanced treatment/refractory chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). A multi-center, open-label, randomized controlled study with 30 patients randomly enrolled in 30mg, 40mg, and 50mg treatment groups first reported the safety, efficacy, and pharmacokinetics (PK) of the drug’s data in CML and Ph+ALL patients outside of China. The results showed that olverembatinib was well tolerated, with strong anti-leukemia activities observed in CML and Ph+ALL patients.
Phase II Clinical Study Results for Olverembatinib
As of April 30, 2022, 41 patients were enrolled in the HQP1351-CC-201 study for CML-CP patients and 23 patients were enrolled in the HQP1351-CC-202 study for CML-AP patients. Preliminary efficacy data showed that 100% of CML-CP patients and 78.3% of CML-AP patients achieved a complete hematological response (CHR) after treatment with olverembatinib, alongside a good tolerability profile.
Five-Year Follow-Up Data for Olverembatinib in China
An open, multicenter Phase I clinical trial evaluated olverembatinib in adult CML-CP or CML-AP patients with a five-year long-term follow-up. From October 26, 2016, to April 30, 2022, a total of 101 patients with CML-CP (n=86) and CML-AP (n=15) were enrolled and received olverembatinib treatment. Preliminary efficacy data showed that 100% of CML-CP patients and 85.7% of CML-AP patients achieved CHR. Most treatment-related adverse events (TRAEs) were Grade 1 or Grade 2, indicating a good safety profile.
Lisaftoclax in CLL/SLL
As of July 4, 2022, 141 patients were enrolled in a Phase II global study for lisaftoclax as a monotherapy or in combination with acalabrutinib or rituximab in naïve relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) patients. No dose-limiting toxicity (DLT) was observed, and no drug interaction was found in the combo group. Preliminary efficacy data showed that 56% of patients recovered to the normal level of lymphocytes rapidly after the end of gradient administration. The objective response rate (ORR) of the monotherapy group, lisaftoclax/acalabrutinib combo group, and lisaftoclax/rituximab combo group was 65% (43 cases), 98% (53 cases), and 87% (23 cases), respectively.
Alrizomadlin in Multiple Myeloma
Alrizomadlin can enhance the anti-tumor activity of pomalidomide in multiple myeloma (MM). The study was displayed on a wall poster at the ASH meeting, with no oral report published.-Fineline Info & Tech
