Live from ASCO 2024 | Updated Data of Bcl-2 Inhibitor Lisaftoclax Combined with Azacitidine in Patients with AML Demonstrate Promising Efficacy and Manageable Safety
The ASCO Annual Meeting showcases the most cutting-edge research in clinical oncology and state-of-the-art advanced cancer therapies and is the world's most influential and prominent scientific gathering of the clinical oncology community. Presenting clinical development progress at the ASCO Annual Meeting for the seventh consecutive year, Ascentage had four clinical studies of three of the company's proprietary drug candidates selected for presentations, including an oral report, at ASCO 2024.
The data of lisaftoclax combined with AZA in elderly/unfit TN patients with AML who were intolerant of standard induction chemotherapies and patients with R/R AML showed excellent therapeutic potential and a favorable safety profile in terms of tumor lysis syndrome (TLS), low incidence of neutropenic fever, and low early mortality.
"As a proprietary novel Bcl-2 inhibitor, lisaftoclax has shown treatment responses comparable to the approved Bcl-2 inhibitor and a better safety profile," said Prof. Jie Jin, a principal investigator of the study from the
"The introduction of Bcl-2 inhibitors represents a major breakthrough for the treatment of AML. However, the hematologic safety issues associated with the approved Bcl-2 inhibitor have limited the clinical adoption and the long-term efficacy," said Dr.
"These efficacy and safety data of lisaftoclax combined with AZA in patients with AML are very encouraging because they reaffirmed the drug's global best-in-class potential as a hopeful new treatment option for patients with AML, a hematologic malignancy commonly associated with a poor prognosis," said Dr.
Highlights of these data presented at ASCO 2024 are as follows:
Safety and efficacy of lisaftoclax, a novel BCL-2 inhibitor, in combination with azacitidine in patients with treatment-naïve or relapsed or refractory acute myeloid leukemia
Abstract#: 6541
Session Title: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Date and Time: June 3, 2024, Monday,
First Author: Huafeng Wang, MD, PhD,
Highlights :
Background and introduction: Early studies showed that lisaftoclax in combination with various agents can synergistically induce apoptosis in AML. This poster presents follow-up safety and efficacy data from a Phase Ib/II study of lisaftoclax combined with AZA in adults with AML.
Patient enrollment and methods:
- This study enrolled elderly (≥75 years)/unfit TN patients with AML who were intolerant of standard induction chemotherapies and patients (≥18 years) with R/R AML. Lisaftoclax (400/600/800 mg) was administered orally once daily in 28-day cycles. In the first treatment cycle, a daily ramp up schedule was used to prevent TLS. AZA was administered once daily on D1-D7 at 75 mg/m2.
- As of
January 25, 2024 , 76 patients with AML were enrolled, including 37 patients with R/R AML and 39 elderly/unfit patients with TN AML who were intolerant of standard induction chemotherapies. The median (range) age was 66 (20-81) years.
Efficacy results:
- In patients with R/R AML treated with lisaftoclax combined with AZA, the overall response rate ([ORR]=CR + CRi + morphologic leukemia-free state [MLFS] + PR) was 72.7%, and the composite complete remission rate (CRc = CR + CRi) was 45.5%. In the 600 mg cohort (n=30), the median duration of treatment was 3.8 months, the ORR was 76.7%, the CRc was 50.0%, the median time to CRc was 2.5 months, the median PFS was 10.2 months, and the median overall survival (OS) was 14.7 months.
- Among patients with TN AML treated with lisaftoclax combined with AZA, the ORR was 64.1%, and the CRc was 51.3%. In the 600 mg cohort (n=29), the median duration of treatment was 3.3 months, and the median time to CRc was 1.9 months. The median PFS and median OS were not reached.
- 600 mg lisaftoclax combined with AZA was established as the recommended Phase II dose (RP2D)
Safety results: All patients treated with lisaftoclax combined with AZA reported treatment-emergent adverse events (TEAEs), with 89.5% experiencing grade 3/4 TEAEs and 43.4% experiencing serious adverse events (SAEs). Common Grade ≥ 3 TEAEs reported in ≥ 10% of patients included neutropenia (57.9%), thrombocytopenia (50.0%), anemia (27.6%), pneumonia (17.1%), and febrile neutropenia (10.5%). No TLS was reported. The 30-day mortality rate was 1.3%.
Conclusions: These data support a promising role for the new Bcl-2 inhibitor lisaftoclax combined with AZA for the treatment of elderly/unfit TN patients with AML intolerant of standard induction chemotherapies and patients with R/R AML, especially given a potentially favorable safety profile in terms of TLS, the incidence of neutropenic fever, and low early mortality. A Phase III randomized, double-blind study is being conducted to determine whether lisaftoclax combined with AZA improves the survival of elderly/unfit TN patients with AML intolerant of standard induction chemotherapies.
*Lisaftoclax is an investigational drug that has not been approved in any country and region.
Appendix: The four clinical studies of
Drug Candidates |
Abstract Title |
Abstract# |
Format |
Olverembatinib |
Updated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) and paraganglioma. |
#11502 |
Oral Report |
Lisaftoclax ( APG-2575 ) |
Safety and efficacy of lisaftoclax, a novel BCL-2 inhibitor, in combination with azacitidine in patients with treatment-naïve or relapsed or refractory acute myeloid leukemia. |
#6541 |
Poster Presentation |
Updated efficacy and safety results of BCL-2 inhibitor lisaftoclax (APG-2575) alone or combined with ibrutinib or rituximab in patients (pts) with Waldenström macroglobulinemia (WM). |
#7078 |
Poster Presentation |
|
APG-2449 |
Updated study results of novel FAK/ALK/ROS1 inhibitor APG-2449 in patients (pts) with non-small-cell lung cancer (NSCLC) resistant to second-generation ALK inhibitors. |
#3124 |
Poster Presentation |
About
Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in
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