On June 18, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that it has released updated data of the Bcl-2 inhibitor lisaftoclax (APG-2575), one of the company’s 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 a poster presentation at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Congress (EHA 2024), taking place in Madrid, Spain (Press release, Ascentage Pharma, JUN 18, 2024, View Source;ascentage-pharma-releases-updated-data-of-lisaftoclax-in-patients-with-rr-mm-and-al-amyloidosis-highlighting-marked-improvement-in-orr-302175033.html [SID1234644431]).

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Building on results from the study released for the first time at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, the updated data presented at EHA (Free EHA Whitepaper) 2024 continued to show impressive efficacy and favorable safety of lisaftoclax-based combinations, particularly the combination with pomalidomide and dexamethasone in R/R MM. Moreover, the study reported an incidence of Grade 3 or higher treatment-related neutropenia of 14.3%, which underscored the regimens’ potential in offering patients a safe new treatment option.

Prof. Sikander Ailawadhi, MD, from Mayo Clinic and the principal investigator of this study, commented, "This is a study of lisaftoclax combined with novel therapeutic regimens in patients with R/R MM or AL amyloidosis. From the primary analysis, it demonstrated that lisaftoclax + pomalidomide in R/R MM could achieve ≥very good partial response (VGPR) rate of 33.3%, and higher VGPR along with increasing lisaftoclax dosage. Moreover, lisaftoclax based therapy in both R/R MM and amyloidosis is very well tolerated with Grade 3/4 neutropenia of 14.3%. This convincing data could provide an alternative treatment option to patients with MM and amyloidosis."

"It is our pleasure to release the updated data of lisaftoclax in patients with R/R MM or AL amyloidosis at this year’s EHA (Free EHA Whitepaper) Hybrid Congress," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "These data underscore the outstanding safety and efficacy profiles of the combination therapies, once again demonstrating these regimens’ global best-in-class potential. We will actively advance this clinical development program to bring patients a safe and effective new treatment option as soon as possible."

The EHA (Free EHA Whitepaper) 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 data on lisaftoclax presented at EHA (Free EHA Whitepaper) 2024 are as follows:

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

Abstract#: P917
Presentation Type: Poster presentation
Topic: Myeloma and other monoclonal gammopathies – Clinical
Date & Time: Friday June 14, 2024, 18:00 – 19:00 CEST
Presenting Author: Prof. Sikander Ailawadhi, Mayo Clinic Florida
Highlights:

Background: R/R MM is incurable, with virtually inevitable relapse without appropriate therapeutic intervention. AL amyloidosis is a rare disease that may cause serious organ damage or death. Lisaftoclax is a novel, potent, selective BCL-2 inhibitor with clinical benefits in hematologic malignancies and solid tumors and a low reported incidence of adverse events (AEs).
Introduction: The aim of this multicenter study was to evaluate the safety and efficacy of lisaftoclax combined with pomalidomide and dexamethasone (Arms A and C) or daratumumab, lenalidomide, and dexamethasone (Arm B) in patients with R/R MM (Arms A and B) or R/R AL amyloidosis (Arm C).
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, 10 patients experienced Grade ≥3 treatment-related adverse events (TRAEs), including neutropenia (14.3%), febrile neutropenia (2.4%). 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), treatment-emergent AE (TEAE, n=3), nonadherence (n=1), or investigator/patient decision (n=5).
Conclusions: Lisaftoclax plus novel therapeutic regimens was well tolerated and demonstrated preliminary antitumor activity in patients with either R/R MM or AL amyloidosis.
*Lisaftoclax is an investigational drug that has not been approved in any country and region.