Lisaftoclax Wins Chinese Approval in Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

China’s National Medical Products Administration (NMPA) has approved lisaftoclax (APG-2575) for the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who received prior treatment with at least 1 systemic therapy, including a BTK inhibitor.¹ The regulatory decision makes lisaftoclax the first BCL-2 inhibitor to earn approval in patients with CLL/SLL in China and the second agent in this class to be approved globally.

The NMPA decision was supported by data from a pivotal phase 2 trial (APG2575CC201; NCT05147467). Findings from the study demonstrated that lisaftoclax met the primary end point of overall response rate (ORR) in patients with relapsed/refractory CLL/SLL who received prior treatment with BTK inhibitors and/or chemoimmunotherapy. The agent also displayed a favorable safety profile; no cases of tumor-lysis syndrome occurred during the trial. Additionally, there was a low incidence of hematologic toxicities, all of which were manageable, and a low rate of nonhematologic toxicities, most of which were grade 1 or 2.

“This approval for the next-generation BCL-2 inhibitor lisaftoclax represents a timely response to the urgent unmet medical need of this patient population, effectively fulfilling the void for BCL-2 inhibitors in CLL/SLL in China,” professor Jianyong Li of the Lymphoma Center at Jiangsu Province Hospital in China and the principal investigator of the trial, stated in a news release.

Lisaftoclax is a novel small-molecule agent that is orally administered and is designed to selectively block BCL-2. This mechanism of action restores normal apoptosis in cancer cells.

The single-arm, open-label, multicenter phase 2 study evaluated lisaftoclax monotherapy in adult patients with relapsed/refractory CLL/SLL who have experienced disease progression on or are intolerant to chemoimmunotherapy and BTK inhibitor treatment.² Patients were required to have a life expectancy of at least 12 weeks and an ECOG performance status of 0 to 2. Eligible patients received oral lisaftoclax at 600 mg daily via 28-day cycles.

The primary end point was ORR. Secondary end points included progression-free survival, time to progression, time to response, duration of response, overall survival, time of half absolute lymphocyte value, maximum plasma concentration, area under the plasma concentration vs time curve, and safety. Other outcome measures consisted of minimal residual disease–negativity rate and BCL-2 expression.

“As the first China-developed BCL-2 inhibitor, lisaftoclax has demonstrated favorable efficacy and a unique safety profile, thus providing clinicians a new treatment option that can meaningfully improve the survival of patients with CLL/SLL. In April 2025, supported by its groundbreaking efficacy and safety data in Chinese patients with CLL/SLL, lisaftoclax was included in the 2025 Chinese Society of Clinical Oncology Guidelines for the Diagnosis and Treatment of Lymphoid Malignancies. The approval and guideline recommendations for lisaftoclax, the only BCL-2 inhibitor approved in China for the treatment of [patients with] CLL/SLL, validated the drug as a safe and efficacious new treatment option, underscoring a major advancement in precision therapy for hematologic malignancies in China,” Li said.¹

Lisaftoclax is under investigation in 4 global phase 3 studies:GLORA (NCT06104566), GLORA-2 (NCT06319456), GLORA-3 (NCT06389292), and GLORA-4 (NCT06641414).

GLORA is examining lisaftoclax in combination with BTK inhibitors in patients with CLL/SLL who previously experienced a suboptimal response with BTK inhibitor therapy following over 12 months of treatment.^1,3 GLORA-2 is evaluating lisaftoclax in combination with acalabrutinib (Calquence) in patients with newly diagnosed CLL/SLL.⁴ In GLORA-3, lisaftoclax plus azacitidine will be examined in patients with acute myeloid leukima.⁵ GLORA-4 is enrolling patients with higher-risk myelodysplastic syndrome and testing lisaftoclax plus azacitidine.⁶

“Our founding team has over 20 years of research experience in the field of apoptosis and accumulated deep expertise on the BCL-2 target,” Dajun Yang, MD, PhD,chairman and chief executive officer of Ascentage Pharma, added in the news release.¹ “This approval for lisaftoclax is a culmination of their dedicated research and a major milestone in our never-ending journey of innovation, further solidifying our leadership in the hematology field. As a proprietary novel drug developed through global innovation, lisaftoclax is a testament to our strength in drug development, bringing much needed change to the global landscape for BCL-2 inhibitors. Moving forward, Ascentage Pharma will remain steadfastly committed to its mission of addressing unmet clinical needs in China and around the world and aspire to bring more innovative therapeutics to more patients globally.”

References

1. Ascentage Pharma announces its novel Bcl-2 inhibitor lisaftoclax approved by China NMPA, ushering in a new era for the treatment of CLL/SLL. News release. Ascentage Pharma. July 10, 2025. Accessed July 11, 2025. https://www.ascentage.com/ascentage-pharma-announces-its-novel-bcl-2-inhibitor-lisaftoclax-approved-by-china-nmpa-ushering-in-a-new-era-for-the-treatment-of-cll-sll/
2. Study of APG-2575 in patients with relapsed/​refractory CLL/​SLL. ClinicalTrials.gov. Updated January 23, 2024. Accessed July 11, 2025. https://clinicaltrials.gov/study/NCT05147467
3. Global trial in APG2575 for patients with CLL/​SLL. ClinicalTrials.gov. Updated February 1, 2024. Accessed July 11, 2025. https://clinicaltrials.gov/study/NCT06104566
4. A global study of lisaftoclax (APG-2575) combined with acalabrutinib versus immunochemotherapy for newly diagnosed CLL/​SLL. ClinicalTrials.gov. Updated May 29, 2024. Accessed July 11, 2025. https://clinicaltrials.gov/study/NCT06319456
5. A pivotal study of APG-2575 (lisaftoclax) combined with azacitidine in the treatment of acute myeloid leukemia.ClinicalTrials.gov. Updated April 2, 2025. Accessed July 11, 2025. https://clinicaltrials.gov/study/NCT06389292
6. Lisaftoclax (APG-2575) combined with azacytidine (AZA) in the treatment of patients with higher-risk myelodysplastic syndrome (GLORA-4). ClinicalTrials.gov. Updated February 19, 2025. Accessed July 11, 2025. https://clinicaltrials.gov/study/NCT06641414