ASCO 2024: Promising Efficacy and Safety of Lisaftoclax with Azacitidine in AML

June 4, 2024 -- Ascentage Pharma, a leading biopharmaceutical company specializing in innovative cancer therapies, chronic hepatitis B (CHB), and age-related diseases, has announced compelling outcomes from a Phase Ib/II trial of its Bcl-2 inhibitor lisaftoclax (APG-2575). The trial assessed the drug's efficacy and safety in combination with azacitidine (AZA) for treatment-naïve (TN) or relapsed/refractory (R/R) acute myeloid leukemia (AML). These findings were presented at the 60th American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL.

The ASCO Annual Meeting is the premier event for clinical oncology, spotlighting groundbreaking research and advanced cancer therapies. This year marked Ascentage Pharma's seventh consecutive participation, with four clinical studies involving three proprietary drugs featured, including an oral presentation.

Study Highlights 

The Phase Ib/II study focused on elderly/unfit TN patients with AML who could not tolerate standard induction chemotherapy and patients with R/R AML. The combination of lisaftoclax with AZA demonstrated significant therapeutic potential, showing a favorable safety profile with minimal tumor lysis syndrome (TLS), low incidence of neutropenic fever, and low early mortality.

Key Findings:
- Therapeutic Efficacy: Lisaftoclax combined with AZA showed notable efficacy in both TN and R/R AML patients. The overall response rate (ORR) for R/R AML patients was 72.7%, with a composite complete remission rate (CRc) of 45.5%. The 600 mg cohort had an ORR of 76.7% and a CRc of 50.0%, with median overall survival (OS) reaching 14.7 months. In TN AML patients, the ORR was 64.1%, and the CRc was 51.3%.
- Safety Profile: The treatment was well-tolerated with a manageable safety profile. Common grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (57.9%), thrombocytopenia (50.0%), and anemia (27.6%). Importantly, no cases of TLS were reported, and the 30-day mortality rate was only 1.3%.

Expert Insights

"Lisaftoclax, as a novel Bcl-2 inhibitor, has demonstrated comparable efficacy to approved Bcl-2 inhibitors but with a superior safety profile, potentially reducing treatment-related mortality and enabling earlier commencement of sequential chemotherapy," commented Prof. Jie Jin from the First Affiliated Hospital, Zhejiang University School of Medicine.

Dr. Huafeng Wang, PhD, echoed these sentiments, highlighting the lesser severity and manageability of hematologic adverse events associated with lisaftoclax. This, he suggested, could significantly enhance the long-term treatment outcomes for AML patients.

Future Directions

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, emphasized the encouraging nature of the Phase Ib/II study results. He noted that a global Phase III trial is already underway to further explore lisaftoclax's potential for improving survival rates in AML patients. Ascentage Pharma remains committed to addressing global unmet clinical needs, with plans to expedite lisaftoclax's clinical development and make it accessible to a broader patient population.

Study Design

The study enrolled 76 AML patients, including 37 with R/R AML and 39 elderly/unfit TN AML patients. Lisaftoclax was administered orally in 28-day cycles at doses of 400/600/800 mg, with a daily ramp-up schedule in the first cycle to mitigate TLS risk. AZA was given daily at 75 mg/m2 on days 1-7 of each cycle.

Conclusion

These findings underscore the promise of lisaftoclax combined with AZA as a new therapeutic option for patients with AML, particularly those who are elderly, unfit, or have relapsed/refractory disease. The combination's efficacy and safety profile suggest it could become a best-in-class treatment for AML, pending further validation from ongoing clinical trials.

Ascentage Pharma continues to advance its mission of developing innovative therapies, with a robust pipeline targeting protein-protein interactions to restore apoptosis and address critical clinical needs globally.

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