Ascentage Pharma Group International announced that it has released updated results from three studies of olverembatinib (HQP1351), the first China-approved third-generation BCR-ABL inhibitor and updated data of lisaftoclax (APG-2575), one of its key drug candidates, combined with novel therapeutic regimens in patients with relapsed/refractory (R/R) multiple myeloma (MM) or immunoglobulin light-chain (AL) amyloidosis, in poster presentations at the 2024 European Hematology Association Hybrid Congress (EHA 2024), taking place in Madrid, Europe. The EHA Hybrid Congress is the largest gathering of the hematology field in Europe. It showcases the most cutting-edge research and state-of-the-art innovative therapies, attracting over 10,000 clinical experts and researchers from more than 100 countries every year.

This year, in addition to the latest data of lisaftoclax, Ascentage Pharma also released those of the third-generation BCR- ABL1 inhibitor olverembatinib (HQP1351) and the EED inhibitor APG-5918. Highlights of the Latest Results from Multiple Clinical Studies of Ascentage Pharma presented at EHA 2024 are as follows: Olverembatinib Overcomes Ponatinib and Asciminib Resistance in Patients (Pts) with Heavily Pretreated Chronic Myeloid Leukemia (CML) and Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Efficacy results: 1) In patients with CML-CP: 31/51 (60.8%) patients achieved a complete cytogenetic response (CCyR), and 25/59 (42.4%) achieved a major molecular response (MMR). No differences in the response rates of patients with/without the T315I mutation were observed.

In patients who failed prior treatment with ponatinib, 15/26 (57.7%) achieved a CCyR (including 10/19 [52.6%] patients with prior resistance to ponatinib and 3/4 [75.0%] with prior intolerance of ponatinib), and 11/30 (36.7%) patients achieved an MMR (including 9/21 [42.9%] patients with prior resistance to ponatinib and 1/6 [16.7%] with prior intolerance of ponatinib). In patients who were asciminib-resistant, 4/8 (50.0%) achieved a CCyR, and 4/12 (33.3%) achieved an MMR. 2) In patients with advanced Ph+ leukemia: 3/14 (21.4%) patients achieved a CCyR, and 3/17 (17.6%) patients achieved an MMR. Safety results: ­ 72 (90.0%) patients experienced treatment emergent adverse events (TEAEs) during their treatment with olverembatinib. Most of the TEAEs were mild to moderate in severity.

­Common grade 3 TEAEs included thrombocytopenia (17.5%), neutropenia (12.5%), and increases in blood creatine phosphokinase (12.5%). Serious adverse events occurring in 3 (3.8%) patients included atrial fibrillation, COVID-19 infection, febrile neutropenia, and intestinal obstruction. No treatment-related adverse events (TRAE) led to death.

Two (2.5%) patients experienced Grade 1 treatment-related arterial occlusive events, one each with angina pectoris and cardiac failure. Lisaftoclax (APG-2575) Combined with Novel Therapeutic Regimens in Patients (Pts) with Relapsed or Refractory (R/R) Multiple Myeloma (MM) or Immunoglobulin Light-Chain (AL) Amyloidosis: Patient enrollment and methods: Patients with an Eastern Cooperative Oncology Group (ECOG) performance status 2 were administered lisaftoclax daily in repeated 28-day cycles. Pomalidomide, daratumumab, and lenalidomide were administered per label use.

Dexamethasone was administered at 40 mg/day, and patients aged >75 were administered at the reduced dose of 20 mg/day. ­ As of January 25, 2024, 44 patients that included 36 patients with R/R MM and 8 patients with R/R AL amyloidosis were enrolled in the 3 arms of the study (Arms A, B, and C) to receive lisaftoclax at various doses. The median (range) age of patients was 70.5 (24-88) years, 68.2% were male, and 65.9% were older than 65 years.

­ The median (range) number of lines of prior therapies was 3 (1-19), median (range) time from diagnosis to the first dose of study drug was 5.5 (1-29) years, and median (range) number of treatment cycles was 4 (1-26). Efficacy results: ­In Arm A, 27 patients with R/R MM were efficacy evaluable. Among them, 10 had partial response (PR), 7 had very good PR (VGPR), and 2 had complete response (CR).

The overall response rate (ORR [PR+VGPR+CR]) was 70.4%. ­In Arm B, 2 patients with R/R MM achieved CR. ­In Arm C, 7 patients with R/R AL amyloidosis were efficacy evaluable, and the ORR was 85.7% (4 VGPRs, 2 CR).

Safety results: ­ Of the 42 patients included in safety analysis, ten patients experienced Grade 3 TRAEs, including neutropenia (14.3%), febrile neutropenia (2.4%), etc. 3 patients experienced serious TRAEs that included febrile neutropenia, acute kidney injury, and diarrhea with electrolyte imbalance (1 each). A total of 24 patients discontinued treatment because of disease progression (n=15), TEAE (n=3), nonadherence (n=1), or investigator/patient decision (n=5).