A study testing the new drug Lisaftoclax for newly diagnosed acute myeloid leukemia(GLORA-3)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ascentage Pharma Group Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2025-05-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ascentage Pharma Group Inc.

External identifiers

EU CT number

2024-516436-10-00

ClinicalTrials.gov

NCT06389292

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

To assess the efficacy of APG-2575 combined with AZA versus placebo combined with AZA in the treatment of patients with newly diagnosed AML who are elderly or ineligible for standard induction chemotherapy (cytarabine and anthracyclines).

Secondary objectives 6

1. To assess whether APG-2575 combined with AZA can improve EFS compared with the control group.
2. To assess overall response rate (ORR), complete response (CR), complete response with incomplete hematologic recovery (CRi), complete response with partial hematologic recovery (CRh), partial response (PR), morphologic leukemia-free state (MLFS)
3. To compare the efficacy between the APG-2575 plus AZA group and the control group in AML patients based on TTR and DOR, etc.
4. To compare the safety between the APG-2575 plus AZA group and the control group in AML patients.
5. To assess population pharmacokinetics (Pop PK) following administration of APG-2575 plus AZA.
6. To assess the effect of APG-2575 plus AZA on quality of life of subjects with newly diagnosed AML who are elderly or ineligible for standard induction chemotherapy through EORTC QLQ C30 (V3) and EuroQol 5 Dimension (EQ-5D) questionnaire.

Conditions and MedDRA coding

Acute myeloid leukemia

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age ≥18 years.
2. Patient must be newly diagnosed with de novo AML based on WHO 2022 Acute Myeloid Leukemia (AML) criteria, and be ineligible for standard chemotherapy (cytarabine and anthracyclines) due to the age or concomitant illness. Elderly AML patient/AML patient intolerant to standard chemotherapy are defined as follows: (1) Age ≥ 70 years or (2) Age ≥ 18 years and < 70 years, and they must meet at least one of the following criteria: • ECOG Performance Status score of 2-3; • Cardiac history of congestive heart failure (CHF) requiring clinical treatment, ejection fraction ≤ 50% or chronic stable angina; • Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in one second (FEV1) ≤ 65%; (See Section 8.2.5) • 30 mL/min ≤ creatinine clearance < 45 mL/min • 1.5 × ULN < total bilirubin ≤ 3.0 × ULN • Other concomitant illnesses that prevent subjects from receiving standard chemotherapy, at the discretion of the investigator, must be reviewed and approved by the sponsor before study enrollment.
3. Life expectancy of ≥ 3 months.
4. Patient who is able to receive oral administration.
5. Patient aged ≥ 70 years with ECOG score of 0-2, or those aged ≥ 18 years and < 70 years with ECOG score of 0-3.
6. Creatinine clearance (CCr) must be ≥ 30 mL/min (calculated using Cockcroft–Gault formula).
7. White blood cell (WBC) count ≤ 30 × 109/L (hydroxycarbamide is allowed to be used to reach this criterion).
8. Liver function: Both ALT and AST ≤ 2.5 × ULN, and total bilirubin ≤ 1.5 × ULN (total bilirubin ≤ 3 × ULN for patients aged ≥ 18 years and < 70 years).
9. Males and females with childbearing potential (only postmenopausal women who have not menstruated for at least 12 months can be considered infertile) who agree to take effective contraceptive measures as confirmed by the investigator throughout the treatment period and at least 6 months after the last dose of the study drug.
10. Patient who is able to understand and voluntarily sign the written informed consent form before any study-specified procedures.
11. Patient must be willing and able to complete study procedures and follow-up examinations.

Exclusion criteria 9

1. Patient diagnosed with acute promyelocytic leukemia (FAB classification of AML-M3 or WHO classification of APL with PML-RAR α or t (9; 22) (q34.1; q11.2); BCR-ABL1-positive AML patients).
2. Active leukemic infiltration of the central nervous system.
3. Active fungal/bacterial/viral infection requiring systemic treatment, including but not limited to HIV antibody positive, HCV antibody or RNA positive, HBsAg positive and HBV-DNA ≥ 2,000 copies/mL (or ≥ 500 IU/mL); those who are suffering from COVID-19 with serious clinical symptoms (subjects who receive injections with COVID-19 vaccine or other live-attenuated vaccines over 28 days before the first dose of the study drug can be enrolled).
4. Use of moderate and/or strong CYP3A4 inducers and/or inhibitors within 7 days prior to the first dose of the study drug.
5. Patient who has been previously treated (including chemotherapy, targeted drugs, monoclonal antibodies and investigational drugs, excluding supportive treatments and hydroxycarbamide) for hematologic disorders, such as AML or MDS.
6. Patient who has a cardiovascular disability status of New York Heart Association (NYHA) Class > 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest, but ordinary physical activity results in fatigue, palpitation, dyspnea or angina pectoris.
7. Subjects who have malabsorption syndrome or other conditions, making them unable to receive enteral administration or resulting in an impact on drug absorption.
8. Subjects who have a history of other malignancies before the start of the study, with the exception of: • Cervical carcinoma in situ or breast cancer in situ after adequate treatment; • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; • Previous malignancies that are not spread, surgically resected (or treated by other means) and clinically cured.
9. Any other condition or circumstance that would, at the discretion of the investigator, make the subject unsuitable for the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS): Interval between the date of randomization to the date of death of any cause. Survival time will be censored at the latest known survival date of the subject if death cannot be confirmed.

Secondary endpoints 9

1. Event-free survival (EFS): The interval from the date of randomization to the time point when any of the following “events” occur (whichever occurs first): • Progressive disease; • Disease recurrence after CR/CRi/CRh/MLFS; • Death of any cause (including but not limited to death caused by leukemia or therapeutic drugs); • CR/CRi/CRh/MLFS is not achieved after at least 6 treatment cycles.
2. Complete response (CR) rate: The proportion of patients with complete response in the total analysis population.
3. Overall response rate (ORR): The proportion of patients who have achieved CR, CRi, CRh, MLFS and PR in total analysis population.
4. Composite complete response (CRc) rate: The proportion of patients who have achieved CR, CRi and CRh in total analysis population.
5. Time to response (TTR): The interval from the date of randomization to the date of the first CR, CRi, or CRh.
6. Duration of response (DOR): The interval from the date of confirming response (CR/CRi/CRh) to the date of disease recurrence or death of any cause (whichever occurs first). DOR will be calculated for patients with the best response of CR, CRh and CRi separately.
7. Safety and tolerability of subjects: Treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) will be evaluated.
8. Population pharmacokinetic (Pop PK) parameters of APG-2575.
9. Results of EORTC QLQ C30 (V3) and EuroQol 5-Dimension (EQ-5D) questionnaire.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ascentage Pharma Group Inc.

Sponsor organisation

Ascentage Pharma Group Inc.

Address

700 King Farm Boulevard

City

Rockville

Postcode

20850-5736

Country

United States

Scientific contact point

Organisation

Ascentage Pharma Group Inc.

Contact name

Yifan Zhai, M.D., Ph.D.

Public contact point

Organisation

Ascentage Pharma Group Inc.

Contact name

Yifan Zhai, M.D., Ph.D.

Third parties 12

Locations

3 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 55 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications