pelcitoclax (APG-1252) / Ascentage Pharma - LARVOL DELTA

Updated study results of pelcitoclax (APG-1252) in combination with osimertinib in patients (pts) with EGFR-mutant non–small cell lung cancer (NSCLC). (ASCO 2022) - P1 | "Osimertinib in combination with targeted therapies has been of clinical interest to improve the outcomes of patients with EGFR-mutant NSCLC. Pelcitoclax plus osimertinib was well tolerated and showed comparable efficacy in TKI-naïve pts. Further randomized control trials are warranted to elucidate the role of pelcitoclax when combined with osimertinib."

Clinical • Combination therapy • IO biomarker • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BCL2 • BCL2L1 • EGFR

BCL-2/BCL-xL inhibitor pelcitoclax with osimertinib for EGFR-mutated advanced non-small-cell lung cancer: a phase 1b trial. (PubMed, J Immunother Cancer) - P1 | "Pelcitoclax combined with osimertinib showed promising safety and antitumor activity in EGFR-mutated NSCLC."

IO biomarker • Journal • P1 data • B Cell Lymphoma • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BCL2 • BCL2L1 • EGFR

Study of Combination APG-1252 Plus Paclitaxel in Patients With Relapsed/Refractory Small Cell Lung Cancer (clinicaltrials.gov) - P1/2; N=58; Recruiting; Sponsor: Ascentage Pharma Group Inc.; Trial primary completion date: Aug 2021 ➔ Aug 2022

Clinical • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Phase1b/2 Trial Of AZA + APG1252 In Patients With High-Risk AML (clinicaltrials.gov) - P1/2 | N=52 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting | Initiation date: Sep 2026 ➔ May 2026

Enrollment open • Trial initiation date • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • BCL2 • BCL2L1 • MECOM

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Pelcitoclax In Patients With Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: M.D. Anderson Cancer Center | N=24 ➔ 0 | Trial completion date: Jun 2032 ➔ Apr 2026 | Initiation date: Aug 2026 ➔ Apr 2026 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Jun 2030 ➔ Apr 2026

Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Trial withdrawal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

Phase1b/2 Trial Of AZA + APG1252 In Patients With High-Risk AML (clinicaltrials.gov) - P1/2 | N=52 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1/2 trial • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • BCL2 • BCL2L1 • MECOM

Combinatorial screen with standard of care and selected anticancer agents identifies multiple combinations with activity against a panel of patient-derived colorectal organoids (AACR 2025) - "Following compound addition, organoid growth was measured by live bright field imaging every 24 h and cell viability was determined by CellTiter-Glo 3D at 48 h and 168 h. Modest responses were observed in most models from the combination of leucovorin with 5-FU; however, >1 log of cytotoxicity was observed in only several models. The panel was more responsive to FOLFOX, which was consistent with the sensitivity of models to oxaliplatin. Responses to TAS-102 varied and >1 log of cytotoxicity was observed in several models...Combination of the BCL-2/BCL-xL inhibitor pelcitoclax plus cobimetinib achieved >1 log of cytotoxicity in most organoid models. Combinations of cobimetinib with the EGFR inhibitors erlotinib, afatinib or cetuximab demonstrated synergy in many organoids according to the Bliss independence model and frequently achieved ≥1 log of cytotoxicity...The combination of cobimetinib and MRTX1133 had synergistic activity by Bliss independence in multiple..."

Clinical • Oncology • BCL2 • BCL2L1 • BRAF • KRAS • PIK3CA

Testing the Combination of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers (clinicaltrials.gov) - P1 | N=42 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

dMMR • Enrollment closed • MSI-H • Platinum resistant • Carcinosarcoma • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Sarcoma • Solid Tumor • Uterine Cancer • BRAF

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

APG-1252 enhances the anticancer role of paclitaxel in non-small-cell lung cancer cells by suppressing the extracellular regulated protein kinases/myeloid cell leukemia 1 pathway. (PubMed, Anticancer Drugs) - "APG-1252 enhanced the anticancer role of PTX in NSCLC cells by suppressing the ERK/MCL-1 pathway. This work provided the theoretical basis for the APG-1252 application."

Journal • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MCL1

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

A Study of APG-1252 Plus Osimertinib(AZD9291) in EGFR TKI Resistant NSCLC Patients (clinicaltrials.gov) - P1 | N=80 | Active, not recruiting | Sponsor: Ascentage Pharma Group Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ADAPT/A2: ALLG AMLM28/A2 (ADAPT): Achieving Durable remissions via Adaptive Pro-survival Targeting in acute myeloid leukaemia (AML)) – VEN/AZA/Pelcitoclax. A therapeutic arm of the ALLG AMLM28 ADAPT Study-Master Protocol. (ANZCTR) - P1/2 | N=50 | Not yet recruiting | Sponsor: Australasian Leukaemia and Lymphoma Group

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • TP53

SYNERGISTIC EFFECTS OF OLVEREMBATINIB (HQP1351) COMBINED WITH BCL-2 INHIBITOR LISAFTOCLAX (APG-2575) AND BCL-2/BCL-XL INHIBITOR PELCITOCLAX (APG-1252) IN T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (T-ALL) (EHA 2025) - "Molecular mechanisms of action were assessed by western blotting.In both T-ALL cell lines, olverembatinib in combination with lisaftoclax or APG-1244 exhibited synergistic antiproliferative effects compared with single agents. Olverembatinib in combination with lisaftoclax and/or pelcitoclax demonstrated synergistic antitumor effects in T-ALL, providing a scientific rationale for further clinical evaluation of this novel combination therapy in patients with this condition."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ANXA5 • BCL2L1 • CASP3 • MCL1 • MYC

Structural, Functional and Inhibitory Annotations of Lumpy Skin Disease Virus Hypothetical Protein LSDV004: An In-Silico Study. (PubMed, Vet Med Sci) - "Molecular docking studies with HDOCK reveal pelcitoclax as exhibiting better docking characteristics compared to other Bcl-2 inhibitors. However, it's important to note that these predictions require validation through wet laboratory experiments to confirm the LSV004 protein's structural, functional and inhibitory properties. These findings suggest LSDV004's role in LSD pathogenesis and its potential as a drug target and also highlight areas for further experimental studies to confirm its function, supporting efforts toward effective treatments and control."

IO biomarker • Journal • Dermatology • BAK1

A Study of APG-1252 Plus Osimertinib(AZD9291) in EGFR TKI Resistant NSCLC Patients (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Ascentage Pharma Group Inc. | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Albumin nanocomplex of BCL-2/xL inhibitor reduced platelet toxicity and improved anticancer efficacy in myeloproliferative neoplasm and lymphoma. (PubMed, Biomaterials) - "Furthermore, Nano-1252 exhibited preferential accumulation in lymphoid organs, leading to enhanced anticancer efficacy in Mantle Cell Lymphoma (MCL) and Myeloproliferative Neoplasms (MPNs) mouse models. Our study not only develops a potential formulation to overcome the current translational barrier of APG-1252 but also reveals novel properties of the well-established albumin nanoformulation, thereby expanding its clinical applications."

Journal • Hematological Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • BCL2

A Study of Pelcitoclax (APG-1252) in Patients With Neuroendocrine Tumors (clinicaltrials.gov) - P1 | N=2 | Terminated | Sponsor: Ascentage Pharma Group Inc. | N=60 ➔ 2 | Recruiting ➔ Terminated; Company Strategy

Enrollment change • Trial termination • Endocrine Cancer • Neuroendocrine Tumor • Solid Tumor • BCL2L2

Combinatorial screen with apoptosis pathway targeted agents alrizomadlin, pelcitoclax, and dasminapant in multi-cell type tumor spheroids. (PubMed, SLAS Discov) - "Apoptosis, or programmed cell death, plays a critical role in maintaining tissue homeostasis by eliminating damaged or abnormal cells. Additionally, interactions were observed from combinations of the apoptosis pathway targeted agents with other agents, including PARP inhibitors, the XPO1 inhibitor eltanexor, and the PI3K inhibitor copanlisib. Enhanced activity was also observed from combinations of the apoptosis pathway targeted agents with MAPK pathway targeted agents, including the MEK inhibitor cobimetinib as well as adagrasib and MRTX1133, which specifically target the KRAS G12C and G12D variants, respectively."

Journal • Brain Cancer • Carcinosarcoma • Lung Cancer • Neurofibrosarcoma • Oncology • Pancreatic Cancer • Rhabdomyosarcoma • Sarcoma • Small Cell Lung Cancer • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • Undifferentiated Pleomorphic Sarcoma • BCL2 • BCL2L1 • KRAS

A clinical study of olverembatinib in combination with APG-1252 for the treatment of relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia or T-cell acute lymphoblastic lymphoma (ChiCTR) - P1 | N=12 | Sponsor: Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University; Shanghai Children's Medical Center, School of Medicine, Shangha

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

Testing the Combination of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2026 ➔ Feb 2027 | Trial primary completion date: Jun 2026 ➔ Feb 2027

Trial completion date • Trial primary completion date • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor • Uterine Cancer • BCL2L1 • BRAF

The novel BCL-2/BCL-XL inhibitor APG-1252-mediated cleavage of GSDME enhances the antitumor efficacy of HER2-targeted therapy in HER2-positive gastric cancer. (PubMed, Acta Pharmacol Sin) - "Mechanistically, APG-1252 combined with lapatinib synergistically induced GSDME-mediated pyroptosis in HER2-positive gastric cancer by activating caspase-dependent pathways and blocking the phospho-AKT/GSK-3β/MCL-1 signaling pathway. Our data indicated that the combination of lapatinib and APG-1252 had a synergistic antitumor effect on HER2-positive gastric cancer through the induction of caspase-3/GSDME-mediated apoptosis and pyroptosis."

IO biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • BCL2 • BCL2L1 • CASP3 • GSDME

Recent clinical data of Pelcitoclax (APG-1252) in combination with osimertinib in the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). (CSCO 2024) - "Study Group: [Organizing Committee]"

Clinical data • Combination therapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

APG-1252 combined with Cabozantinib inhibits hepatocellular carcinoma by suppressing MEK/ERK and CREB/Bcl-xl pathways. (PubMed, Int Immunopharmacol) - "Our findings suggest that APG-1252 in combination with Cabozantinib offers a more effective treatment strategy for HCC patients, warranting further clinical investigation."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • BCL2 • BCL2L1

In-silico characterization of LSDV132 protein divulged its BCL-2-like nature. (PubMed, Heliyon) - "The docking results revealed that pelcitoclax exhibited best docking scores i.e., -9.1841 kcal/mol, among all of the other docked complexes. This fact signified that this compound might serve as an inhibitor of LSDV132 protein."

Journal • Dermatology • BCL2