Global Registrational Phase III Study of Bcl-2 Inhibitor Lisaftoclax in Treatment-Naïve Patients with CLL/SLL Approved by the China CDE

Ascentage Pharma a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) has approved a global pivotal registrational Phase III study designed to evaluate a key drug candidate in Ascentage Pharma's pipeline, Bcl-2 inhibitor APG-2575 (Lisaftoclax), in combination with the Bruton's tyrosine kinase (BTK) inhibitor acalabrutinib, versus immunochemotherapy in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), aiming to validate the combination regimen as a first-line treatment for CLL/SLL. This approval marks another major milestone in the clinical development of the drug candidate following the clearance from the US Food and Drug Administration (FDA) in August 2023 for the global registrational Phase III study in patients with CLL/SLL who have received prior therapies. This global multi-center, randomized-controlled, open-label, pivotal Phase III confirmatory trial (APG2575CC301) is designed to evaluate the efficacy and safety of APG-2575 (lisaftoclax) combined with acalabrutinib versus immunochemotherapy in treatment-naïve patients with CLL/SLL.

CLL/SLL is a hematologic malignancy caused by mature B-cell neoplasms. It primarily affects older populations and is among the most common leukemia subtypes in adults, accounting for a quarter of all leukemia cases in the Western World, with over 100,000 new diagnoses reported globally each year¹. In China, CLL/SLL is occurring at a rapidly rising incidence rate, with a younger age of onset and higher aggressiveness², thus posing a serious threat to public health in the country. Advancements in basic research and targeted therapies have brought significant survival benefit to patients with CLL/SLL. However, CLL/SLL still presents major clinical challenges and urgent medical needs for new treatment options that can offer both efficacy and safety.

APG-2575 (Lisaftoclax) is a novel, orally administered small-molecule Bcl-2 selective inhibitor being developed by Ascentage Pharma to treat the patients with malignancies by selectively blocking the antiapoptotic protein Bcl-2 and hence restoring the normal apoptosis process in cancer cells. With strong global best-in-class potential, lisaftoclax is the first Bcl-2 inhibitor in China and the second anywhere globally that has demonstrated compelling clinical activity and entered a pivotal registrational study. At present, lisaftoclax is being evaluated in multiple clinical studies across the world and more than 300 patients with CLL/SLL have already been treated with the drug either as a monotherapy or in combinations. Interim results suggest that lisaftoclax offers potent efficacy to patients with CLL/SLL and has the potential as a safe, efficacious, and convenient treatment option.

The preliminary results from a global Phase II study have already showed therapeutic potential of lisaftoclax in combination with acalabrutinib, with an objective response rate (ORR) of 98% in patients with relapsed/refractory (R/R) CLL/SLL, an ORR of 100% in treatment-naïve patients with CLL/SLL, and an excellent safety profile that is on par with that of lisaftoclax monotherapy. In the study, lisaftoclax was initiated on a daily ramp-up that simplified the dosing schedule and allowed patients receive the treatment dose more quickly³. Moreover, the study adopted a dosing regimen that was improved on that of existing Bcl-2 inhibitor plus BTK inhibitor combinations as it eliminated the lead-in for the BTK inhibitor, thus allowed patients to begin receiving the combination therapy more quickly. Those results were being released as an Oral Presentation at the 2022 American Society of Hematology (ASH) Annual Meeting.

"In earlier studies, lisaftoclax combined with acalabrutinib has already demonstrated impressive efficacy and safety, validating the combination regimen's therapeutic potential and its promise as a patient-centric treatment strategy," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "We are very encouraged by this approval for the global registrational Phase III study of lisaftoclax combined with acalabrutinib. In terms of the dose ramp-up schedule for the Bcl-2 inhibitor and no lead-in of the BTK inhibitor, this trial adopts an innovative and optimized dosing regimen that is more convenient and allows for a faster onset of actions compared to studies of similar combinations. Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will vigorously advance those clinical programs of lisaftoclax to expedite the drug's journey to market for the benefit of more patients."

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