On June 7, 2022 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that it has released the updated results from a Phase Ib/II study of the Bcl-2 inhibitor lisaftoclax (APG-2575) in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) in a Poster Presentation at the 58th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Ascentage Pharma, JUN 7, 2022, View Source;ascentage-pharma-releases-updated-data-demonstrating-lisaftoclaxs-apg-2575-therapeutic-potential-in-patients-with-rr-cllsll-301563282.html [SID1234615726]).
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Entering the fifth consecutive year in which company’s abstracts were selected for presentations by the ASCO (Free ASCO Whitepaper) Annual Meeting, Ascentage Pharma showcased results from multiple clinical trials of its five drug candidates, including favorable data of lisaftoclax, a key drug candidate of the company’s apoptosis-targeted pipeline, in Chinese patients with R/R CLL/SLL showing an objective response rate (ORR) of 67.4%. Lisaftoclax was well tolerated, and all adverse events were manageable. No dose-limiting toxicity (DLT) were observed at up to 800 mg/day. The risk of clinical tumor lysis syndrome (TLS) in patients on daily dose ramp-up was minimal.
Prof. Jianyong Li, Director of the Hematology Department, Jiangsu People’s Hospital, and the principal investigator of this study, said, "Lisaftoclax is a Bcl-2 selective inhibitor that can induce apoptosis and suppress the growth of tumor cells. In this Phase Ib/II study, lisaftoclax as a single agent showed favorable preliminary efficacy and safety, and a daily ramp-up schedule that is patients’ friendly. We look forward to further evaluating the efficacy of lisaftoclax as a single agent and in combinations in patients with R/R CLL/SLL."
Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, "Lisaftoclax is the first China-developed Bcl-2 inhibitor entering clinical development in China, also the world’s second and China’s first Bcl-2 inhibitor being investigated in pivotal trials. Data released at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting suggest that lisaftoclax may offer an effective, safe, and more ‘user friendly’ treatment alternative to patients with R/R CLL/SLL. We are taking firm steps forward with this clinical development program to allow patients to benefit from this novel therapeutic as soon as possible. Meanwhile, we are also evaluating lisaftoclax monotherapy and combinations in patients with solid tumors."
Dr. Zhai continued, "Furthermore, we are proud to be able to present clinical development progress for a number of Ascentage Pharma’s drug candidates, which highlight our capabilities in global innovation. Honoring our mission of addressing unmet clinical needs in China and around the world, we are now accelerating our clinical programs to bring more safe and effective therapeutics to patients in need."
The highlights of this abstract on lisaftoclax are as follows:
A phase Ib/II study of lisaftoclax (APG-2575), a novel BCL-2 inhibitor (BCL-2i), in patients (pts) with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL).
Abstract: #7543
The aim of this multicenter, open-label study was to evaluate the safety, antitumor activity, PK, and pharmacodynamics (PD) of lisaftoclax in Chinese patients with R/R CLL/SLL.
As of January 25, 2022, 45 patients had been enrolled. Lisaftoclax was administered orally once daily at 3 dose cohorts (400, 600, or 800 mg) in 28-day cycles, with 15 patients in each cohort.
Lisaftoclax monotherapy demonstrated favorable safety profiles in all three dose cohorts, and no DLT was observed during the Phase I study.
The risk of TLS in patients on daily dose ramp-up was extremely low, which was consistent with the observations of the Phase I study. The median duration of treatment was 7 cycles. and the ORR in the 43 efficacy evaluable patients with R/R CLL/SLL was 67.4%, including 1 complete response (CR) and 28 partial responses (PRs).
BCL-2i lisaftoclax was well tolerated up to 800 mg/day. There were no significant new or unmanageable safety findings. The recommended Phase II dose (RP2D) of lisaftoclax was determined as 600 mg. Lisaftoclax may offer a treatment alternative for patients with R/R CLL/SLL, with a daily ramp-up schedule that may be more convenient and "user friendly".
Appendix: A list of Ascentage Pharma’s abstracts selected by this year’s ASCO (Free ASCO Whitepaper) Annual Meeting