lisaftoclax (APG-2575) / Ascentage Pharma - LARVOL DELTA

Updated Results from a Phase 1b study of olverembatinib (HQP1351) combined with lisaftoclax (APG-2575) in pediatric patients with relapsed/refractory Philadelphia Chromosome–Positive acute lymphoblastic leukemia (ASH 2025) - P1 | "Patients received olverembatinib monotherapy (40 mg adult-equivalent dose [AED], every other day, days 1–14), followed by combination therapy with lisaftoclax (200, 400, or 600 mg AED daily, with 3-day dose ramp-up) and dexamethasone (6 mg/m²/day, days 15–42). Importantly, these outcomes were achieved without intensive chemotherapy or immunotherapy, highlighting this novel combination as an effective orally active and chemotherapy-free treatment option for this high-risk pediatric population. The study is ongoing for further efficacy and safety assessments and regimen optimization."

Clinical • P1 data • Acute Lymphocytic Leukemia • CNS Disorders • Epilepsy • Hematological Malignancies • Leukemia • Neutropenia • Pediatrics • Thrombocytopenia • ABL1

BCL-2 inhibition in North American adult T-cell leukemia/lymphoma: Preclinical insights and early clinical outcomes (ASH 2025) - "Hence, we evaluated thepreclinical efficacy of BCL-2 inhibitors in NA ATLL cells and explored clinical outcomes in chemotherapy-refractory ATLL patients.Preclinical:A panel of well-characterized North American patient-derived ATLL cell lines [Pt-4a, Pt-5a, Pt-6a, Pt-15a]along with Japanese patient-derived ATLL cell lines [ATL43T (−)] (J-ATLL) were used to evaluate the efficacyof different BCL-2 inhibitors, including Venetoclax, Sonrotoclax, and Lisaftoclax. Both North American and Japanese ATLL cell lines have shown preclinical sensitivity to BCL-2inhibition using Venetoclax and other emerging inhibitors. Distinct molecular dependencies identifiedthrough BH3 profiling and transcriptional analyses. Venetoclax induces mitochondrial apoptosis anddownregulates key HTLV-1 viral oncogenes, targeting both survival pathways and viral factors."

Clinical data • IO biomarker • Preclinical • Adult T-Cell Leukemia-Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • BCL2L1 • CASP3 • CD4 • MCL1 • NOTCH1 • TP53

Results of the APG2575AU101 Study of lisaftoclax (APG-2575) combined with azacitidine (AZA) in patients with newly diagnosed (ND) or prior venetoclax–exposed myeloid malignancies (ASH 2025) - P1/2 | "Mostof the mutations detected in EOT samples were related to the RTK–RAS–MAPK pathway of generegulation, indicating that tumors may commonly exhibit adaptive responses to treatment pressure,involving both reactivation of signaling pathways and resistance reprogramming. ClinicalTrials.gov ID:NCT04964518."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia • ABCB1 • CHEK2 • CSF3R • DNMT3A • GNAS • IDH2 • PMS2 • RUNX1 • SRSF2 • TEK • TET2 • TP53

Results of a registrational Phase 2 study of lisaftoclax monotherapy for treatment of patients (pts) with Relapsed/Refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who had failed Bruton's tyrosine kinase inhibitors (BTKis) (ASH 2025) - P2 | "Although venetoclax monotherapy isapproved (ex-China) to treat pts with CLL/SLL who have a 17p deletion [del(17p)] (Davids MS et al, ClinLym Mye Leuk. Forty (53.2%) pts experienced grade ≥ 3 AEs related to the study drug (TRAEs), includingdecreased neutrophil (27.3%), decreased platelet (16.9%), and white blood cell (7.8%) counts; anemia(9.1%), and infectious pneumonitis (3.9%). No tumor lysis syndrome was reported, and no lisaftoclax-related deaths occurred.ConclusionIn this study, we show that lisaftoclax monotherapy achieved significant ORR and long-lasting PFS with anacceptable safety profile in pts with heavily-treated R/R CLL/SLL refractory to BTKis."

Clinical • IO biomarker • Monotherapy • P2 data • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Small Lymphocytic Lymphoma • CD20 • IGH • TP53

Advances in the Management of Relapsed/Refractory CLL and Richter Transformation (ICML 2025) - P=N/A, P2, P3 | "BRUIN CLL-321 is a phase 3, registrational study that evaluated pirtobrutinib compared to the investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) [23]...Nemtabrutinib is now being evaluated in the registrational, phase 3 BELLWAVE-010 trial (NCT05947851) for patients with R/R CLL, comparing nemtabrutinib plus venetoclax to venetoclax plus rituximab...An ongoing, open-label, first-in-human phase 1/2 study is evaluating the BTK degrader BGB-16673 as monotherapy in patients with R/R CLL [27, 28]...NX-2127 is an investigational, first-in-class BTK degrader currently being evaluated in a phase 1 trial for patients with relapsed or refractory B-cell malignancies, CLL [29, 30]...NX-5948 is another investigational and more selective BTK degrader in an ongoing Phase 1a/1b clinical trial...This trial aims to establish lisaftoclax plus acalabrutinib as a potential alternative to venetoclax-based BTKi combination..."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2L1 • TP53

Pirtobrutinib, Lisaftoclax, and Rituximab in the Treatment of R/R DLBCL (clinicaltrials.gov) - P2 | N=29 | Recruiting | Sponsor: The First Affiliated Hospital of Soochow University

New P2 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ASH 2025 | Ascentage Pharma Presents Encouraging Data from Phase Ib/II Study of Bcl-2 Inhibitor Lisaftoclax in Venetoclax–Exposed Patients with Myeloid Malignances (GlobeNewswire) - "In the 44 evaluable patients with R/R AML/MPAL, the ORR was 43.2%, and the CR rate was 31.8% (14/44). In the 22 evaluable patients with venetoclax–exposed R/R AML/MPAL, the ORR was 31.8% (7/22), and the CR rate was 22.7% (5/22). In the 15 evaluable patients with ND HR MDS/CMML, the ORR was 80.0%, including 6 (40.0%) patients who achieved a CR, and 6 (40.0%) who achieved a marrow CR (mCR). Median overall survival (OS) values for patients with R/R AML/MPAL or R/R HR MDS/CMML were 7.6 months and 11.3 months, respectively."

P1/2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Myelodysplastic Syndrome

The Development of Novel Therapies for Chronic Lymphocytic Leukaemia in the Era of Targeted Drugs. (PubMed, J Clin Med) - "Over the past decade, chronic lymphocytic leukaemia (CLL) treatment has shifted from chemoimmunotherapy to targeted oral agents, predominantly Bruton's tyrosine kinase inhibitors (BTKis) and the BCL-2 inhibitor venetoclax...This has driven the development of novel therapeutic strategies, including non-covalent BTKis such as pirtobrutinib and nemtabrutinib, which retain activity in BTK C481-mutated disease. Next-generation BCL-2 inhibitors (sonrotoclax, lisaftoclax) and BTK degraders are promising in early clinical trials...Minimal residual disease (MRD)-guided, fixed-duration regimens represent a significant paradigm shift toward personalised treatment and potentially deeper remissions. Ongoing clinical studies are expected to introduce new effective therapies that may further transform the management of CLL in the coming years."

IO biomarker • Journal • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Ascentage Pharma Presents Pivotal China Registrational Study Data for Lisaftoclax in Oral Report at 2025 American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "In the data featured in the oral report, Lisaftoclax monotherapy demonstrated durable efficacy and manageable safety in patients with heavily pretreated BTK-refractory R/R CLL/SLL, with no tumor-lysis syndrome (TLS) observed. Notably, among the 77 enrolled patients, 33 (42.9%) had chromosomal complex karyotype, 30 (39%) had del(17p)/TP53 mutation, and 41 (53.2%) had unmutated IGHV....Lisaftoclax achieved a 62.5% objective response rate (ORR) in heavily pretreated, BTKi-refractory patients, nearly half with complex karyotype. Lisaftoclax monotherapy demonstrated a median progression-free survival of 23.89 months in patients with heavily pretreated BTK-refractory R/R CLL/SLL, with no tumor lysis syndrome reported."

P2 data • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Orelabrutinib Plus Lisaftoclax and Rituximab in Untreated Mantle Cell Lymphoma With High-Risk Disease (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Ruijin Hospital

New P2 trial • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • BCL2

Lisaftoclax (APG-2575) Combined with Novel Therapeutic Regimens in Patients (pts) with Relapsed or Refractory Multiple Myeloma (R/R MM) or Immunoglobulin Light‑Chain (AL) Amyloidosis (ASH 2024) - P1/2 | "This study evaluated the safety and efficacy of lisaftoclax combined with pomalidomide and dexamethasone (Pd; Arm A) or daratumumab, lenalidomide, and dexamethasone (DRd; Arm B) in R/R MM and lisaftoclax combined with Pd in R/R AL amyloidosis (Arm C). These combination therapies demonstrated a favorable safety profile with no drug-drug interactions, particularly in hematologic side effects. ClinicalTrials.gov registration : NCT04942067; internal study identifier : APG2575MU101."

Clinical • Acute Kidney Injury • Amyloidosis • Anemia • Constipation • Endocrine Disorders • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukopenia • Metabolic Disorders • Multiple Myeloma • Musculoskeletal Pain • Nephrology • Neutropenia • Oncology • Renal Disease • Thrombocytopenia

First Report on the Effects of Lisaftoclax (APG-2575) in Combination with Novel Therapeutic Regimens in Patients with Relapsed or Refractory Multiple Myeloma (R/R MM) or Immunoglobulin Light-Chain (Amyloid Light-Chain [AL]) Amyloidosis (ASH 2023) - P1/2 | "Methods This multicenter study evaluated lisaftoclax combined with pomalidomide and dexamethasone (Arms A and C) or daratumumab, lenalidomide, and dexamethasone (Arm B) in patients with R/R MM (Arm A and B) or R/R amyloidosis (Arm C). Conclusion Lisaftoclax, combined with novel therapeutic regimens, was well tolerated and has demonstrated preliminary antitumor activity in patients with AL amyloidosis or R/R MM. Internal study identifier: APG-2575-MU101; clinical trial registration: NCT04942067."

Clinical • Combination therapy • Acute Kidney Injury • Amyloidosis • Anemia • Chronic Lymphocytic Leukemia • Constipation • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Multiple Myeloma • Musculoskeletal Pain • Nephrology • Neutropenia • Oncology • Rare Diseases • Renal Disease • Solid Tumor • Thrombocytopenia

Abbv-453: A Highly Potent and Selective Next Generation Small Molecule Inhibitor of BCL-2 (ASH 2024) - P1 | "ABBV-453 demonstrated superior growth inhibition of the RS4; 11 xenograft compared to both sonrotoclax or lisaftoclax at equivalent doses and schedule. ABBV-453 has the potential to be the best-in-class next-generation BCL-2 inhibitor and is actively being investigated in phase 1 clinical trials in relapsed or refractory (R/R) MM (ClinicalTrials.gov ID, NCT05308654) and R/R CLL/SLL (NCT06291220)."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • ANXA5 • BCL2 • BCL2L1 • BCL2L2 • CASP3 • CASP7 • MCL1

Lisaftoclax (APG-2575) Demonstrates Activity and Safety When Given with Accelerated Ramp-up and then Combined with Acalabrutinib or Rituximab in Patients (pts) with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Including Those with Prior Exposure to Venetoclax (ASH 2024) - P1, P3 | "We continue to accrue pts with prior ven exposure to further evaluate this promising signal. A global registrational phase 3 study GLORA (NCT06104566) is recruiting."

Clinical • IO biomarker • Anemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Thrombocytopenia • IGH • TP53

Olverembatinib (HQP1351) in Combination with Lisaftoclax Overcomes Venetoclax Resistance in Preclinical Model of Acute Myeloid Leukemia (AML) (ASH 2024) - "Introduction The combination of BCL-2 inhibitor venetoclax with hypomethylating agents (HMAs) or low-dose cytarabine is widely used in treatment of patients with newly diagnosed AML who are elderly or ineligible for intensive chemotherapy. This combination downregulated signaling pathways shown to mediate venetoclax resistance. These promising findings suggest that this strategy may provide a new therapeutic option for patients with venetoclax-resistant AML, an urgent unmet medical need."

Combination therapy • IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • CASP3 • FGFR • FLT3 • MCL1

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 (ASH 2023) - P1/2 | "For the first time, we present the safety, pharmacokinetics (PK), and efficacy of lisaftoclax alone or combined with azacitidine (AZA) or homoharringtonine (HHT), in adults with AML, MDS, or other myeloid neoplasms. This ongoing trial continues to enroll pts. Internal study (CT.gov) identifier: APG2575AC101 (NCT04501120)."

Clinical • Acute Myelogenous Leukemia • Anemia • Cardiovascular • Chronic Lymphocytic Leukemia • Chronic Myelomonocytic Leukemia • Congestive Heart Failure • Endocrine Disorders • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Myelodysplastic Syndrome • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

Updated Efficacy and Safety Results of Lisaftoclax (APG-2575) in Patients (Pts) with Heavily Pretreated Chronic Lymphocytic Leukemia (CLL): Pooled Analyses of Two Clinical Trials (ASH 2023) - P1, P1/2 | "CR/CRi exhibited a trend of positive correlation with escalating dose levels. No significant new or unmanageable safety findings were observed."

Clinical • Anemia • Chronic Lymphocytic Leukemia • Dyslipidemia • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertriglyceridemia • Leukemia • Oncology

Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor, in Combination with Azacitidine in Treatment of Patients with Myelodysplastic Syndrome (MDS) (ASH 2024) - P1/2 | "Internal study identifier : APG2575AC101. Clinicaltrials.gov identifier : NCT04501120."

Clinical • Combination therapy • IO biomarker • Anemia • Febrile Neutropenia • Infectious Disease • Myelodysplastic Syndrome • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia • ASXL1 • RUNX1 • TET2 • TP53

APG-2449, a Novel Focal Adhesion Kinase (FAK) Inhibitor, Exhibits Antileukemic Activity and Enhances Lisaftoclax (APG-2575)-Induced Apoptosis in Acute Myeloid Leukemia (AML) (ASH 2024) - "This novel combination showed antileukemic activity in both BCL-2 inhibitor-sensitive and -insensitive AML cells in vitro and in xenograft models. Overall, these promising results provide a novel approach in the clinical development of lisaftoclax for treatment of patients with AML."

IO biomarker • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor • ALK • ANXA5 • BCL2L1 • MCL1 • STAT3

Safety and Efficacy of Olverembatinib (HQP1351) Combined with Lisaftoclax (APG-2575) in Children and Adolescents with Relapsed/Refractory Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia (R/R Ph+ ALL): First Report from a Phase 1 Study (ASH 2024) - P1 | "Dexamethasone 6 mg/m2/day was administered orally QD from D15-42. This regimen resulted in promising CR rates without intensive chemotherapy or immunotherapy. The study is currently in the dose-expansion phase."

Clinical • IO biomarker • P1 data • Acute Lymphocytic Leukemia • Anemia • CNS Disorders • Epilepsy • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pediatrics • Thrombocytopenia • ABL1 • BCR

Results of the APG2575AU101 study of lisaftoclax (APG-2575) combined with azacitidine (AZA) in patients with newly diagnosed (ND) or prior venetoclax–exposed myeloid malignancies (GlobeNewswire) - "Ascentage Pharma to Present Data...at ASH 2025....In the 47 evaluable patients with R/R AML/MPAL, the ORR was 40.4%, the complete response (CR) rate was 29.8% (14/47). In the 24 patients with venetoclax–exposed R/R AML/MPAL, the ORR was 29.2% (7/24), the CR rate was 20.8% (5/24). In the 15 evaluable patients with ND HR MDS/CMML, the ORR was 80.0%, including 6 (40.0%) patients who achieved a CR, and 6 (40.0%) who achieved a marrow CR (mCR). Median overall survival (OS) values for patients with R/R AML/MPAL or R/R HR MDS/CMML were 7.6 months and 11.3 months, respectively."

P1/2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Myelodysplastic Syndrome

Results of a registrational phase 2 study of lisaftoclax monotherapy for treatment of patients (pts) with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who had failed Bruton’s tyrosine kinase inhibitors (BTKis) (GlobeNewswire) - "Ascentage Pharma to Present Data...at ASH 2025....As of July 25, 2025, among 72 evaluable patients with R/R CLL/SLL, the ORR as confirmed by the independent review committee (IRC) was 62.5%, the median progression-free survival (mPFS) was 23.89 months (with a median follow-up of 22.01 months). Among high-risk patients (those with adverse prognostic genotypes such as del(17p)/TP53 mutation, chromosomal complex karyotype, and unmutated IGHV), the treatment showed clinically meaningful deep responses. 21.8% of patients achieved minimal residual disease (MRD) negativity in peripheral blood. In the 11 evaluable patients with bone marrow MRD, 6 achieved MRD-negativity."

P2 data • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

BCL-2 inhibition in Waldenström macroglobulinaemia and marginal zone lymphoma. (PubMed, Br J Haematol) - "We also summarize the preclinical and ongoing clinical experience with BCL-2 inhibitors, such as venetoclax, sonrotoclax, lisaftoclax and LOXO-338. BCL-2 inhibitors have emerged as safe and effective treatment options for treating patients with MZL and WM."

Journal • Review • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

Safety, tolerability, and pharmacokinetics of lisaftoclax (APG-2575)-based therapy in patients with chronic lymphocytic leukemia: Phase 1b/2 study. (PubMed, Med) - P1 | "Daily ramp-up over 5-7 days (to 400 or 800 mg) with continuous treatment with lisaftoclax alone or plus rituximab or acalabrutinib was well tolerated and led to responses in patients with CLL without clinically significant pharmacokinetic interactions."

Journal • P1/2 data • PK/PD data • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Novel Coronavirus Disease • Oncology • Small Lymphocytic Lymphoma • Thrombocytopenia

Lisaftoclax: First Approval. (PubMed, Drugs) - "Lisaftoclax received its first approval on 10 July 2025 in China for the treatment of chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) in adult patients who had received at least one prior systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor. This article summarizes the milestones in the development of lisaftoclax leading to this first approval for CLL/SLL."

Journal • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Disorders • Leukemia • Lymphoma • Oncology • Small Lymphocytic Lymphoma