Ascentage Pharma announced that results from three clinical studies of lisaftoclax (APG-2575), a key candidate drug in the Company's pipeline, have been selected for presentations at the 65thAmerican Society of Hematology (ASH) Annual Meeting, marking the second consecutive year in which clinical results of lisaftoclax were selected. This year, results from multiple clinical studies on two of Ascentage Pharma's lead drug candidates (olverembatinib and lisaftoclax) have been selected for presentations at the ASH Annual Meeting. Developed by Ascentage Pharma, lisaftoclax is an orally available Bcl-2 inhibitor with a wide therapeutic window in multiple hematologic malignancies and solid tumors.

The investigational clinical data of lisaftoclax in patients with chronic lymphocytic leukemia (CLL), to be presented at the ASH Annual Meeting this year, once again demonstrate the drug's efficacy and favorable tolerability in patients with CLL who were heavily pretreated and had prior exposure to BTK inhibitors. In two other abstracts on lisaftoclax, results were disclosed from clinical studies of the drug as a single agent and in combination regimens in multiple hematologic malignancies, including relapsed/refractory (R/R) multiple myeloma (MM) and acute myeloid leukemia (AML). The ASH Annual Meeting is one of the larger gatherings of the international hematology community, bringing together the latest and most cutting-edge scientific research in the pathogenesis and clinical treatment of hematologic diseases.

The 65th ASH Annual Meeting will take place on December 9-12, 2023, both online and in-person, in San Diego, CA (United States). Updated Efficacy and Safety Results of Lisaftoclax (APG-2575) in Patients (pts) with Heavily Pretreated Chronic Lymphocytic Leukemia (CLL): Pool Analysis of Two Clinical Trials: Highlights: This abstract reported updated data from long-term follow-ups in two Phase 1b/2 studies of lisaftoclax (APG-2575-CN001 [NCT03913949] and APG-2575-CC101 [NCT04494503]) in patients with CLL. In the 2 studies, lisaftoclax was administered orally once daily in 28-day cycles, in 100 mg, 200 mg, 400 mg, 600 mg, and 800 mg dose cohorts.

Under close monitoring for prevention and early detection of tumor lysis syndrome (TLS), patients were treated (with a daily dose ramp-up schedule) until disease progression, intolerable toxicity, death, or any other reason for termination. As of April 27, 2023, a total of 47 patients with CLL were enrolled. The median (range) duration of follow-up was 14.06 (0.70-30.2) months.

The median (range) age was 58 (34-80) years. At enrolment, 53.2% of patients were in Rai stage III/IV, and 48.9% of patients were in Binet stage C. 44.7% of patients had received =3 lines of treatment; 66.0% of patients had received =2 lines of treatment; 23.4% of patients were treated with Bruton tyrosine kinase inhibitors (BTKis); and 55.3% were treated with a CD20 monoclonal antibody. 68.1% (32) of patients discontinued the study due to disease progression (51.1%), consent withdrawal (6.4%), adverse events (AEs) (2.1%), investigator's decision (2.1%), poor compliance (2.1%), protocol deviation (2.1%), and other reasons (2.1%).

The overall response rate (ORR) in patients with CLL was 73.3% (33/45), and the complete response (CR)/incomplete hematological recovery (Cri) rate was 24.4% (11/45). In total, 76.6% (36) of patients experienced grade =3 treatment-emergent adverse events (TEAEs); 27.7% (13) experienced serious AEs (SAEs). Treatment-related adverse events (TRAEs) were observed in 95.7% (45) of patients, of whom 68.1% (32) experienced grade =3 TRAEs and 14.9% (7) experienced SAEs.

One incident of TLS was reported. Conclusions: Lisaftoclax demonstrated significant efficacy and favorable tolerability in patients with CLL who were heavily pretreated and had prior exposure to BTKis. Safety and Efficacy of Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor (BCL-2i), in Relapsed or Refractory (R/R) or Treatment-Naïve (TN) Patients (Pts) with Acute Myeloid leukemia (AML), Myelodysplastic Syndrome (MDS), or Other Myeloid Neoplasms: Highlights: This multicenter, open-label, Phase 1 study in China evaluated the efficacy and safety of lisaftoclax alone or combined with azacitidine (AZA) or homoharringtonine (HHT) in patients with treatment-naïve or R/R AML, MDS, or other myeloid neoplasms. Trial design: In part one, lisaftoclax as a single agent was orally administered once daily at 200, 400, 600, or 800 mg, using a "3+3" dose escalation design.

In part two, patients with R/R AML, mixed-phenotype acute leukemia (MPAL), blastic plasmacytoid dendritic cell neoplasm (BPDCN), or chronic myelomonocytic leukemia (CMML) were enrolled in Cohorts A, B, and C; while patients with higher-risk MDS were enrolled in Cohort D; and older or chemotherapy-ineligible (unfit) patients with treatment-naïve AML were enrolled in Cohort E. Lisaftoclax was administered orally once daily in 28-day cycles (or 14-day cycles for patients with MDS). A daily ramp-up schedule was adopted to prevent TLS. Cohort A was treated with lisaftoclax combined with low-dose HHT (1 mg daily on days [d] 1-14); Cohort B was treated with lisaftoclax combined with standard-dose HHT (2 mg/m2 daily on d1-7); Cohort C, D, E were treated with lisaftoclax combined with AZA (75 mg/m2 daily on d1-7).

Dose-limiting toxicity (DLT) was assessed during the first cycle. As of July 19, 2023, a total of 115 patients were enrolled, including 89 patients with AML (64 R/R; 25 TN older/unfit), 22 with MDS (7 R/R MDS; 15 TN MDS), 2 MPAL, 1 CMML, and 1 BPDCN. A total of 13 patients received lisaftoclax monotherapy and 102 patients received combination regimens.

Efficacy results: In patients treated with lisaftoclax monotherapy, the ORR and composite remission rate (CRc=complete remission [CR] + CR with incomplete blood count recovery [CRi]) were each 8.3% (1/12). Lisaftoclax at 600 mg and 800 mg were chosen as exploratory doses for combination therapies. Among the 21 efficacy evaluable patients with TN AML in Cohort E, the ORR and CRc were 71.4% and 47.6%, respectively.

Among the 36 efficacy evaluable patients with R/R AML or myeloid neoplasm in Cohort C, the ORR and CRc were 75.0% and 44.4%, respectively. The progression-free survival (PFS) was 10.22 months. Among patients in Cohort B, the ORR and CRc were both 75.0%.

Among patients in Cohort D, the ORR was 70.0%, the CR/marrow CR rate was 60.0%.