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

Phase 3

Recruiting

• Conditions: Higher-risk Myelodysplastic Syndrome
• Interventions: Drug: Lisaftoclax (APG-2575); Drug: Azacitidine Injection; Other: Placebo

• Registration Number: NCT06641414
• Lead Sponsor: Ascentage Pharma Group Inc.

Brief Summary

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.

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 Timeline

• Study First Submitted: 2024-10-12
• Study First Submitted QC: 2024-10-12
• Study First Posted: 2024-10-15
• Study Start: 2025-01-22
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-18
• Last Update Posted: 2025-02-19
• Primary Completion: 2029-06
• Study Completion: 2029-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 464

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 7 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lisaftoclax (APG-2575) combined with Azacitidine	Azacitidine Injection	-
Placebo combined with Azacitidine	Azacitidine Injection	-
Lisaftoclax (APG-2575) combined with Azacitidine	Lisaftoclax (APG-2575)	-
Placebo combined with Azacitidine	Placebo	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (2)

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China