Lisaftoclax (APG-2575) Combined With Azacytidine (AZA) in the Treatment of Patients With Higher-risk Myelodysplastic Syndrome (GLORA-4).

A Global Multicenter, Double-blind, Randomized, Registrational Phase 3 Study of Lisaftoclax (APG-2575) in Combination With Azacitidine (AZA) in Patients With Newly Diagnosed Higher Risk Myelodysplastic Syndrome (HR-MDS) (GLORA-4).

A global multicenter, randomized, double-blind, placebo-controlled, pivotal phase III study. To evaluate overall survival (OS) of Lisaftoclax (APG-2575) combined with azacitidine (AZA) vs. placebo combined with azacitidine in newly diagnosed patients with HR-MDS.

Study Overview

• Status: Recruiting
• Conditions: Higher-risk Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Lisaftoclax (APG-2575); Drug: Azacitidine Injection; Other: Placebo

Detailed Description

This study intends to enroll patients with HR-MDS to receive the therapy of Lisaftoclax (APG-2575) combined with azacitidine (AZA) or placebo combined with azacitidine.

• Study Type: Interventional
• Enrollment (Estimated): 490
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yifan Zhai, M.D., Ph.D.; Phone Number: +86-20-28068501; Email: yzhai@ascentage.com
• Study Contact Backup: Name: Qian Niu, M.D.; Email: Qian.Niu@ascentage.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100033
      • Recruiting
      • Peking University People's Hospital
      • Contact: Xiaojun Huang, M.D.,Ph.D.; Phone Number: 010-88325229; Email: xjhrm@medmail.com.cn
      • Principal Investigator: Xiaojun Huang, M.D.,Ph.D.
• United States
  • Texas
    • Houston, Texas, United States, 77054
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Guillermo Garcia-Manero, M.D.; Phone Number: 713-745-3428; Email: ggarciam@mdanderson.org
      • Principal Investigator: Guillermo Garcia-Manero, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Newly diagnosed higher-risk MDS.
2. ECOG score of ≤2.
3. Expected survival ≥ 3 months.
4. Adequate organ function.
5. Female subjects of potential childbearing potential have a negative urine or serum pregnancy test before dosing. Subjects of childbearing potential as well as their partners voluntarily use contraception deemed effective by the investigator during the treatment period and for at least six months after the last dose of study drug.
6. Able to understand and voluntarily sign a written informed consent form, which must be signed prior to the performance of any trial-specified study procedures.
7. Subjects are able to complete study procedures and follow-up examinations.

Exclusion Criteria:

1. Concomitant other malignancies or prior malignancies with disease-free intervals of less than 1 year at the time of signing the informed consent.
2. Have undergone hematopoietic stem cell transplantation.
3. Uncontrolled active infection
4. Use of moderately potent inducers and moderately potent inhibitors of CYP3A4 within 14 days prior to the first dose of study drug.
5. MDS or other conditions that cannot be administered enterally.
6. Any condition that the subject is deemed to be inappropriate to participate in this study after evaluation by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lisaftoclax (APG-2575) combined with Azacitidine	Drug: Lisaftoclax (APG-2575); QD, oral administration.; Drug: Azacitidine Injection; QD, hypodermic or intravenous injection.
Active Comparator: Placebo combined with Azacitidine	Drug: Azacitidine Injection; QD, hypodermic or intravenous injection.; Other: Placebo; QD, oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival（OS）	The primary endpoint was overall survival (OS), defined as the time from the date of randomization to the date of death of any cause.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation based on the adverse event concurrence	Number of treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) will be evaluated.	Up to 5 years

Collaborators and Investigators

• Sponsor: Ascentage Pharma Group Inc.
• Investigators: Study Chair: Guillermo Garcia-Manero, M.D., M.D. Anderson Cancer Center; Study Chair: Xiaojun Huang, M.D., Ph.D., Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: October 12, 2024
• First Submitted That Met QC Criteria: October 12, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Lisaftoclax; Higher-risk Myelodysplastic Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Syndrome; Preleukemia; Myelodysplastic Syndromes; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; Lisaftoclax
• Other Study ID Numbers: APG2575MG301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No