ASCO 2024: Ascentage Pharma's Lisaftoclax Shows Promising Efficacy and Safety in WM Patients

SUZHOU, China, and ROCKVILLE, Md., June 4, 2024 — Ascentage Pharma (6855.HK), a global biopharmaceutical company, has unveiled new data from its global Phase Ib/II trial of the Bcl-2 inhibitor lisaftoclax (APG-2575) for treating Waldenström macroglobulinemia (WM). The findings were presented at the 60th American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL, marking the second consecutive year the study has been selected for the conference.

The ASCO Annual Meeting is a premier event for clinical oncology, presenting the latest advancements in cancer research and treatment. Ascentage Pharma, participating for the seventh consecutive year, featured four clinical studies of its proprietary drugs, including an oral presentation.

The updated results from the lisaftoclax study underscore the drug's safety and efficacy as both a monotherapy and in combination treatments. Key data revealed that when combined with ibrutinib, lisaftoclax achieved a 90.9% objective response rate (ORR) in treatment-naïve WM patients, with manageable adverse events and a low risk of tumor lysis syndrome (TLS). Furthermore, no drug-drug interactions were noted with ibrutinib.

"Lisaftoclax is a selective Bcl-2 inhibitor designed to induce apoptosis in cancer cells," explained Dr. Sikander Ailawadhi from Mayo Clinic, the study's Principal Investigator. "In this global trial involving relapsed/refractory WM patients, lisaftoclax demonstrated favorable efficacy, unaffected by the CXCR4 mutation. The drug also showed a tolerable safety profile with a low risk of TLS."

Dr. Yifan Zhai, Ascentage Pharma’s Chief Medical Officer, highlighted the significance of the data presented at ASCO 2024. "Lisaftoclax is a pioneering Bcl-2 inhibitor, the first of its kind at a pivotal stage in China and the second globally. The clinical data emphasizes its potential as a treatment for hematologic malignancies. We aim to advance its development to benefit more patients soon."

The study's highlights include:
- Efficacy and Safety: The trial included 46 WM patients divided into three treatment arms. Arm A received lisaftoclax monotherapy, Arm B combined lisaftoclax with ibrutinib, and Arm C combined it with rituximab. The ORRs were 41.7% for Arm A, 90.9% for Arm B, and 37.5% for Arm C. Arm A patients with the wild-type CXCR4 gene responded better than those with the mutation, whereas Arms B and C showed no significant differences based on CXCR4 status.
- Safety Profile: The study found manageable adverse events, with grade 3 TLS in some cases due to pre-existing conditions like renal impairment and dehydration. Severe adverse events (grade ≥ 3) included neutropenia, thrombocytopenia, and anemia. No ventricular arrhythmia was observed, and the maximum tolerated dose was not reached.
- Pharmacokinetics: Lisaftoclax combined with ibrutinib showed similar pharmacokinetic exposure to the drugs administered separately, indicating no significant drug-drug interactions.

Ascentage Pharma continues to focus on developing innovative therapies for cancer and other serious diseases. Their research emphasizes inhibiting protein-protein interactions to promote apoptosis or programmed cell death. The company is running over 40 Phase I/II trials globally, including five Phase III studies.

Ascentage Pharma has garnered multiple designations for its drug candidates, notably olverembatinib, which has received Priority Review and Breakthrough Therapy Designations in China, and Orphan Drug and Fast Track Designations in the US and EU.

The company aims to bolster its research capabilities and accelerate clinical development to address unmet medical needs globally.

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