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

作者：Tapan M. Kadia, Patricia Kropf, Michael F. Leahy, Chong Chyn Chua, Shaun Fleming, Caspian Oliai, John Kwan, Chun Yew Fong, Joshua Richmond, Paul Cannell, James Dugan, Maria R. Baer, Stephen Ting, Daniel Egan, Zi Chen, Qian Niu, Mingyu Li, Divya Mekala, Zhiyan Liang, Mohammad Ahmad, Yifan Zhai · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-1641 · 被引用次数：2 · 研究领域：Acute Myeloid Leukemia Research、Protein Degradation and Inhibitors、Myeloproliferative Neoplasms: Diagnosis and Treatment

Abstract Introduction Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) have poor prognoses. Venetoclax plus hypomethylating agent AZA is approved for certain patients with AML, but most have resistance or intolerance, warranting additional therapies for post-venetoclax relapsed/refractory (R/R) AML. Lisaftoclax, a novel, oral, investigational small-molecular BCL-2 inhibitor, has shown enhanced treatment responses when combined with AZA in preclinical and clinical studies. The aim of this study was to assess the safety and efficacy of lisaftoclax plus AZA for hematologic malignancies. Methods APG2575AU101, a phase 1b/2, multicenter, open-label trial (initiated on July 30, 2021), enrolled patients diagnosed with histologically confirmed R/R AML, mixed phenotype acute leukemia (MPAL), chronic myelomonocytic leukemia (CMML), or R/R higher-risk (HR) MDS (by 2016 WHO classification) for which no available standard therapies were indicated or expected to elicit a durable response. These comprised patients with ND or R/R disease, including prior venetoclax treatment. In part 1, oral lisaftoclax (200-800 mg QD) plus AZA was administered to assess DLTs and MTD. In part 2, lisaftoclax (200/400/600 mg QD) over 28 or 14 days of 28-day cycles was administered with standard-dose AZA. Outcome measures included DLT (by NCI CTCAE v5.0) assessed within the first 28-day cycle of study treatment, MTD, RP2D, overall response rate (ORR), and overall survival (OS). Results As of the ...