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

Lisaftoclax (APG-2575):…Upcoming milestones (GlobeNewswire) - "(i) Plan to initiate clinical studies to confirm Lisaftoclax’s potential to overcome venetoclax resistance in patients who have failed venetoclax treatment; (ii) Continue to advance enrollment in GLORA, GLORA-2, GLORA-3, GLORA-4 trials; (iii) Plan to actively advance the inclusion of Lisaftoclax in China’s National Reimbursement Drug List (NRDL) in 2026."

New trial • Reimbursement • Trial status • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Lisaftoclax (APG-2575):…Commercial progress (GlobeNewswire) - "Commercial sales of Lisaftoclax commenced in China on July 25, 2025 as the first batch of prescriptions were filled on July 25, 2025 shortly after receiving approval on July 10, 2025 from China’s National Medical Products Administration (NMPA) for the treatment of adult patients with CLL/SLL....Revenue from sales of Lisaftoclax was US$10.1 million for 2025 for the five-month period from August 2025 to December 2025."

Sales • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Sonrotoclax (BGB-11417), a selective Bcl-2 inhibitor, demonstrates better efficacy than Venetoclax (Ven) and Lisaftoclax (APG-2575) in hematological cancer cells, xenografts, and human bloods (AACR 2026) - "Son demonstrates significant advantage over Ven and Lisa in preclinical studies, including better efficacy in Bcl-2-dependent cancers, against Bcl-2-G101V and BTK resistance mutations, and enhanced target engagement in human whole blood. These highlight Son's great potential in addressing unmet needs in hematologic malignancies."

Clinical • IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CASP3

Efficacy and Safety of Lisaftoclax (APG-2575) Monotherapy in Patients With Indolent Lymphoma (clinicaltrials.gov) - P2 | N=75 | Not yet recruiting | Sponsor: Henan Cancer Hospital

Monotherapy • New P2 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Oncology

A Phase 1 Study Of FLAG Chemotherapy In Combination With Lisaftoclax And Pelcitoclax In Patients With Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1 trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

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

A Prospective, Single-Arm, Multicenter Study on the Efficacy and Safety of Lisaftoclax Combined with Rituximab and Lenalidomide Regimen in the Treatment of Previously Untreated Elderly Patients with Mantle Cell Lymphoma (ChiCTR) - P=N/A | N=40 | Not yet recruiting | Sponsor: Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University; Jiangsu Province Hospital, The First Affiliated Hospital of Na

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

Lisatoclax Plus R-CHOP or Pola-R-CHP in Untreated DLBCL: A Phase Ib/II Study (clinicaltrials.gov) - P1/2 | N=122 | Not yet recruiting | Sponsor: Sun Yat-sen University

New P1/2 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2

Lisaftoclax (APG-2575) Safety and Activity As Monotherapy or Combined with Acalabrutinib or Rituximab in Patients (pts) with Treatment-Naïve, Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (R/R CLL/SLL): Initial Data from a Phase 2 Global Study (ASH 2022) - P1 | "Seventeen (12%) pts had progressed on BTKi (n = 15) and/or after venetoclax (n = 3) therapy. Conclusions The RP2D of lisaftoclax was 600 mg daily. Initiated with a daily dose ramp-up, lisaftoclax alone or combined with acalabrutinib or rituximab had a manageable safety profile and was active in pts with treatment-naïve or R/R CLL/SLL."

Clinical • IO biomarker • Monotherapy • P2 data • Anemia • Chronic Lymphocytic Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Metabolic Disorders • Nephrology • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Pain • Renal Disease • Small Lymphocytic Lymphoma • Thrombocytopenia • IGH • TP53

Phase 1b/2 study of lisaftoclax (APG-2575) combined with azacitidine (AZA) in patients (pts) with treatment-naïve (TN) or prior venetoclax (VEN)-exposed myeloid malignancies. (ASCO 2025) - P1/2 | "LISA at different dose regimens combined with AZA provides promising treatment options for pts with HR-MDS or AML. No DLTs occurred. The MTD was not reached."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia

Clinical Study on Efficacy and Safety of G-CSF Combined with Azacitidine and Venetoclax in the Treatment of Adult Acute Myeloid Leukemia (ChiCTR) - P=N/A | N=34 | Not yet recruiting | Sponsor: The Second Affiliated Hospital of Guangxi Medical University; The Second Affiliated Hospital of Guangxi Medical University

New trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

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

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

Safety and efficacy of lisaftoclax, a novel BCL-2 inhibitor, in combination with azacitidine in patients with treatment-naïve or relapsed or refractory acute myeloid leukemia. (ASCO 2024) - P1/2 | "Our data support an emerging role for this new BCL-2 inhibitor Lisa combined with AZA for the treatment of elderly/unfit TN and R/R AML pts, especially with low early mortality and promising mPFS. A phase 3, randomized, double-blind clinical study is in progress to determine whether Lisa + AZA improves OS in elderly/unfit pts with AML. *HW, XW, and YL are co-first authors."

Clinical • Combination therapy • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

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

Ramping up the express stairs: Lisaftoclax in CLL. (PubMed, Med) - "Lisaftoclax, a next-generation BCL2 inhibitor, demonstrated promising efficacy and safety in the phase 1b/2 APG2575CU101 trial by Davids et al. in chronic lymphocytic leukemia (CLL).1 With rapid dose ramp-up and high response rates across monotherapy and combination cohorts, including high-risk and previously treated populations, lisaftoclax shows potential as an effective therapeutic option for CLL, pending validation in larger trials."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

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

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

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