pelcitoclax (APG-1252)

P1, N=80, Active, not recruiting, Ascentage Pharma Group Inc. | Recruiting --> Active, not recruiting

P1/2, N=50, Not yet recruiting, Australasian Leukaemia and Lymphoma Group

P1, N=80, Recruiting, Ascentage Pharma Group Inc. | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

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.

P1, N=2, Terminated, Ascentage Pharma Group Inc. | N=60 --> 2 | Recruiting --> Terminated; Company Strategy

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.

P1, N=12, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University; Shanghai Children's Medical Center, School of Medicine, Shangha

P1, N=42, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Feb 2027 | Trial primary completion date: Jun 2026 --> Feb 2027

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.

Our findings suggest that APG-1252 in combination with Cabozantinib offers a more effective treatment strategy for HCC patients, warranting further clinical investigation.

P1, N=42, Recruiting, National Cancer Institute (NCI) | Initiation date: Feb 2024 --> Sep 2023

Our data demonstrate that pelcitoclax has antitumor activity and is well tolerated, supporting its further clinical development for human solid tumors, particularly combined with agents that downregulate MCL-1.