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

Surzetoclax: A Potentially Best-In-Class BCL-2 Inhibitor for the Treatment of Multiple Myeloma with T(11;14) Translocation or High BCL-2 Expression (IMS 2026) - P1/2 | "TGI of the RS4;11 model was superior to that achieved with clinically relevant BCL-2 inhibitors venetoclax, sonrotoclax or lisaftoclax at equivalent doses and schedules...Importantly, surzetoclax combined effectively with daratumumab and dexamethasone in the KMS-27 and the BCL-2 high RPMI-8226 MM xenograft models. These data identify surzetoclax as a potential best-in-class, next-generation BCL-2 inhibitor that is in a phase-1/-2 clinical trial for the treatment of patients with R/R MM (ClinicalTrials.gov ID: NCT06953960)."

IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • ANXA5 • BCL2L1 • BCL2L2 • MCL1

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

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

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

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

Study of Mitoxantrone, Cytarabine and Lisaftoclax Combination Therapy for Newly Diagnosed Adult Acute Myeloid Leukemia (ChiCTR) - P2 | N=60 | Not yet recruiting | Sponsor: The first affiliated hospital of guangzhou university of Chinese medicine; The first affiliated hospital of guangzhou university of Chinese medicine

New P2 trial • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

BH3 Mimetics as Models for Precision Apoptosis Targeting: Functional Dependence, Adaptive Survival Networks, and Trial Design in Hematologic Malignancies (SOHO 2026) - "The BH3 mimetics venetoclax and lisaftoclax provide important models for understanding how lineage context, apoptotic priming, microenvironmental signaling, and adaptive resistance shape outcomes...MURANO follow-up confirmed durable benefit with venetoclax-rituximab in relapsed/refractory CLL, while the CLL14 trial demonstrated sustained PFS and measurable residual disease negativity-associated durability with venetoclax-obinutuzumab in untreated CLL... BH3 mimetics teach a broader lesson for precision oncology: Target presence is not target dependence. Durable benefit requires functional biomarker selection, rational combinations that anticipate adaptive survival rewiring, and trial designs that measure resistance evolution before clinical relapse. Future trials should incorporate functional apoptotic profiling, serial resistance assessment, and disease-specific combination strategies to improve patient selection, deepen responses, reduce toxicity, and extend the..."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Leukemia • Lymphoma • Multiple Myeloma • Oncology • BCL2 • BCL2L1

Safety and Preliminary Efficacy of Olverembatinib (HQP1351) Combined With Lisaftoclax (APG-2575) in Children and Adolescents With Relapsed/Refractory Philadelphia-Positive Acute Lymphoblastic Leukemia: Results of a Phase 1b Study (SOHO 2026) - P1 | "Olverembatinib plus lisaftoclax induced rapid, deep remissions in pediatric R/R Ph+ ALL with manageable toxicity and favorable pharmacokinetics. This chemotherapy-free oral regimen demonstrated activity across ABL1 mutants with CNS penetration, supporting its potential in this high-risk population. ABL1: ABL proto-oncogene 1, non-receptor tyrosine kinase, ALL: acute lymphoblastic leukemia, BCL-2: B-cell lymphoma 2, BCR::ABL1: breakpoint cluster region–Abelson 1, CNS: central nervous system, CR: complete response, FISH: fluorescence in situ hybridization, MRD: measurable residual disease, T315I: threonine-to-isoleucine mutation at position 315."

Clinical • IO biomarker • P1 data • Acute Lymphocytic Leukemia • B Cell Lymphoma • Leukemia • Lymphoma • Oncology • ABL1 • BCR

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

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

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

HLA-AML: Homoharringtonine, Lisaftoclax, and Azacitidine for AML After Venetoclax-Based Therapy Failure (clinicaltrials.gov) - P2 | N=73 | Enrolling by invitation | Sponsor: Guangdong Second Provincial General Hospital

New P2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2

RPLM-RS: Rituximab, Pirtobrutinib, Lisaftoclax and Liposomal Mitoxantrone for for Richter Syndrome Transformed From CLL (clinicaltrials.gov) - P2 | N=23 | Not yet recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China

New P2 trial • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Richter's Syndrome • BCL2

Lisaftoclax in Combination with Daunorubicin and Cytarabine for Newly Diagnosed Acute Myeloid Leukemia: A Prospective, Single-Arm, Phase 2 Clinical Study (ChiCTR) - P2 | N=55 | Not yet recruiting | Sponsor: Blood Diseases Hospital, Chinese Academy of Medical Sciences; Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Scienc

New P2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Single-center, Prospective, Exploratory Clinical Study (clinicaltrials.gov) - P=N/A | N=30 | Not yet recruiting | Sponsor: LanZhou University

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

Study for Safety and Efficacy of Olverembatinib Combined With APG-2575 in Children With Relapsed/Refractory Ph + ALL (clinicaltrials.gov) - P1 | N=19 | Recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China | Trial completion date: Dec 2024 ➔ Dec 2027 | Trial primary completion date: Aug 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

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 the GLORA, GLORA-2, GLORA-3, and GLORA-4 trials; (iii) Plan to actively advance the inclusion of Lisaftoclax in China’s NRDL in 2026."

Enrollment status • New trial • Reimbursement • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Myelodysplastic Syndrome • Small Lymphocytic Lymphoma

APG115XC103: APG-115 Alone or in Combination With APG-2575 in Recurrent or Refractory Neuroblastoma or Solid Tumors (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Ascentage Pharma Group Inc. | Phase classification: P1 ➔ P1/2 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Phase classification • Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor

RR-AML-2023: Multicenter, Platform-type Clinical Study of Refractory/Recurrent Acute Myeloid Leukemia (clinicaltrials.gov) - P=N/A | N=458 | Recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China | N=120 ➔ 458 | Trial completion date: Jun 2026 ➔ Jun 2028 | Trial primary completion date: Jan 2026 ➔ Jan 2028

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Case Report: A unique case of Philadelphia chromosome-positive mixed-phenotype acute leukemia with active Epstein-Barr virus infection in a kidney transplantation recipient. (PubMed, Front Oncol) - "A tailored therapeutic strategy was implemented, combining olverembatinib with dexamethasone, lisaftoclax and azacitidine for leukemia treatment, alongside B-cell-depleting therapy with rituximab for EBV viremia. This integrated approach successfully induced hematologic remission and achieved clearance of EBV viremia, providing a potential therapeutic framework for managing this complex dual condition. To our knowledge, this is the first reported case of this specific clinical triad, highlighting the significant therapeutic challenges posed by the coexistence of these conditions."

Journal • Epstein-Barr Virus Infections • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Nephrology • Oncology • Transplantation

Efficacy and Safety of Lisaftoclax (APG-2575) Monotherapy in Patients With Mature B-cell Lymphoma (clinicaltrials.gov) - P2 | N=75 | Not yet recruiting | Sponsor: Henan Cancer Hospital | Initiation date: Mar 2026 ➔ Jul 2026 | Trial primary completion date: Jan 2027 ➔ Jul 2027

Monotherapy • Trial initiation date • Trial primary completion date • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

BV-LISA-CTCL: Efficacy and Safety of Brentuximab Vedotin Combined With Lisaftoclax in CD30+ Cutaneous T-cell Lymphoma (CTCL) (clinicaltrials.gov) - P2 | N=46 | Not yet recruiting | Sponsor: Peking University First Hospital

New P2 trial • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • TNFRSF8

A Phase Ib Dose-Finding and Safety Study of Lisaftoclax Combined with a Pediatric-Inspired Chemotherapy Regimen in Adult Acute Lymphoblastic Leukemia (ALL) (ChiCTR) - P1 | N=30 | Not yet recruiting | Sponsor: The First Hospital of China Medical University; The First Hospital of China Medical University

New P1 trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia

Multicenter, Prospective, Single-Arm Phase II Study of Lishatoclax Plus Decitabine in Patients With Myelodysplastic Neoplasms Who Have Failed Venetoclax Therapy (ChiCTR) - P2 | N=24 | Not yet recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.; Institute of Hematolog

New P2 trial • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Multicenter randomized controlled superiority trial of lisaftoclax + idarubicin + cytarabine versus idarubicin + cytarabine in the treatment of newly diagnosed acute myeloid leukemia (ChiCTR) - P=N/A | N=298 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Army Medical University; The First Affiliated Hospital of Army Medical University

Head-to-Head • New trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology