A Worldwide Study Testing the New Drug Lisaftoclax for Patients with Newly Diagnosed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (GLORA-2).

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]

Trial duration

22 Aug 2025 → ongoing

Decision date (initial)

2025-02-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ascentage Pharma Group Inc.

External identifiers

EU CT number

2024-514084-26-00

ClinicalTrials.gov

NCT06319456

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To evaluate the progression‑free survival (PFS) of Lisaftoclax in combination with acalabrutinib versus immunochemotherapy in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) determinated by Independent Review Committee (IRC).

Secondary objectives 6

1. Key secondary objective: To compare the PFS of Lisaftoclax in combination with acalabrutinib versus immunochemotherapy in patients with CLL/SLL determinated by investigator assessments.
2. Other secondary objectives:To compare the overall survival (OS) of Lisaftoclax in combination with acalabrutinib versus immunochemotherapy in patients with CLL/SLL
3. To compare the efficacy of Lisaftoclax in combination with acalabrutinib versus immunochemotherapy in patients with CLL/SLL including overall response rate (ORR), time to response (TTR), and duration of response (DOR) determinated by IRC and investigators
4. To compare the efficacy of Lisaftoclax in combination with acalabrutinib versus immunochemotherapy in patients with CLL/SLL as measured by minimal residual disease (MRD) negativity rate in peripheral blood and/or bone marrow.
5. To evaluate the safety of Lisaftoclax in combination with acalabrutinib versus immunochemotherapy in patients with CLL/SLL.
6. To evaluate the population pharmacokinetic of Lisaftoclax in combination with acalabrutinib.

Conditions and MedDRA coding

Newly Diagnosed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age ≥18 years
2. Diagnosed with CLL/SLL based on IWCLL NCI-WG guidelines (2018 Edition) and indicating at least one of the criteria for treatment (see Appendix 14: Treatment Criteria).
3. Measurable disease (peripheral blood lymphocyte ≥ 5 × 109/L, or enlargement of lymph nodes (baseline LDi ≥ 1.5 cm), or hepatomegaly or splenomegaly caused by CLL/SLL).
4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2
5. QT interval corrected using the Fridericia's formula (QTcF) on electrocardiogram (ECG): QTcF≤450 ms in males or ≤470 ms in females
6. Adequate bone marrow function independent of growth factor support (no growth factor used within 7 days before the first dose of the study drug) and independent of blood transfusion (no whole blood transfusion or blood component transfusion supportive therapy within 7 days before the first dose of the study drug) as follows:  Absolute neutrophil count (ANC) ≥ 1.0 × 109/L (ANC ≥ 0.5 × 109/L specified in patients with bone marrow involvement of CLL/SLL)  Platelet count ≥ 50 × 109/L;  Hemoglobin ≥ 8.0 g/dL.
7. Adequate hepatic, renal, and coagulation functions as follows:  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × Upper Limit of Normal (ULN), serum total bilirubin ≤ 1.5 × ULN;  Serum creatinine ≤ 1.5 × ULN. If serum creatinine > 1.5 × ULN, creatinine clearance (CrCL) must be ≥ 50 mL/min;  International normalized ratio (INR), activated partial thromboplastin time (APTT), and prothrombin time (PT) ≤ 1.5 × ULN.
8. Males and females of childbearing potential (only postmenopausal women who have not menstruated for at least 12 months or those surgically sterilized can be considered infertile) and their partners voluntarily take effective contraceptive measures throughout the treatment period and at least 3 months after the last dose of the study drug. Male patients must avoid sperm donation from the first dose of the study drug to three months after the last dose of the study drug.
9. Female patients of childbearing potential have negative serum pregnancy test results within approximately 14 days prior to the first dose of the study drug. If the serum pregnancy test results available are > 7 days from the first dose, urine pregnancy test results before the first dose of the study drug must be negative.
10. Patients must be able to understand and voluntarily sign a written informed consentthat has been approved by the Ethics Committee (EC) before any screening or study-specific procedure
11. Patients must be willing and able to complete study procedures and follow-up examinations

Exclusion criteria 16

1. Any previous CLL/SLL-specific treatments (excluding corticosteroids for necessary immediate intervention; only a maximum daily equivalent dose of prednisone less than or equal to 20 mg is allowed within 10 days before starting the study treatment).
2. TP53 mutation or del (17p).
3. Transformation to invasive Non-Hodgkin’s lymphoma (e.g., Richter’s transformation, prolymphocytic leukaemia or diffuse large B-cell lymphoma) or leukaemia involving the central nervous system. If Richter’s transformation is suspected, PET-CT or biopsy should be performed to rule it out.
4. Use of any of the following treatments within 14 days or 5 half-lives before the first dose of the study drug, or clinically significant adverse reactions/toxicities that are related to previous treatments not recovered to < Grade 2: Anti-tumor therapies include chemotherapy, radiotherapy, anti-tumor steroid treatment, anti-tumor Chinese medicine treatment; investigational treatment including targeted small molecule drugs.
5. Use of the moderate to strong CYP3A inhibitors, such as fluconazole, ketoconazole and clarithromycin, within 7 days or 5 half-lives (whichever is shorter) before the first dose of the study drug; or use of strong CYP3A inducers, such as rifampicin, carbamazepine, phenytoin, and St. John's wort, within 14 days before the first dose of the study drug.
6. Failure to fully recover adequately from prior surgical procedures at the discretion of the investigator. Patients who receive a major surgery within 28 days prior to the first dose of the study drug or who receive a minor surgery (excluding biopsy) within 14 days prior to the initiation of the study
7. Presence of significant cardiovascular diseases, such as symptomatic arrhythmia, congestive heart failure, myocardial infarction, or any New York Heart Association (NYHA) grade 3 or 4 cardiovascular disease within 6 months before study entry. Note: Patients with controlled, asymptomatic atrial fibrillation are allowed to participate in this study.
8. A history of significant renal, neurological, psychiatric, pulmonary, endocrine, metabolic, immune, cardiovascular, or hepatic disease, which will have an adverse effect on the patient if he/she participates in the study, at the discretion of the investigator. Those requiring intervention for any of the above diseases in the past 6 months must be discussed by the investigator and the sponsor.
9. Patients who require warfarin (potential drug-drug interactions may increase exposure to warfarin and related complications) or other anticoagulants or active hemorrhage occur within 2 months before study entry
10. Known to have hypersensitivity to ingredients or analogues of drugs used in the study
11. Pregnant or lactating female patients and patients who are expected to become pregnant during the study period or within 3 months after the last dose.
12. Patients who have history of other active malignant tumor other than CLL/SLL within 3 years before study entry, except for: • Adequately treated carcinoma in situ of cervix uteri • Completely resected basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin • Confinement and resection of previously cured malignancies (or other treatments). Note: If patients stopped antitumor treatment for ≥3 years and there was no tumor recurrence for ≥3 years prior to joining the study, these patients could be enrolled.
13. Malabsorption syndrome or other conditions not suitable for enteral administration.
14. Other clinically significant uncontrolled symptoms, including but not limited to: uncontrolled active systemic infection (virus, bacteria or fungi), known clinically active hepatitis B or C, or HIV infection.
15. Primary active autoimmune and connective tissue diseases, such as active and uncontrolled primary autoimmune cytopenia, including autoimmune hemolytic anemia (AIHA) and primary immune thrombocytopenia (ITP).
16. Any other condition or circumstance that would, at the discretion of the investigator, make the patient unsuitable for the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. IRC-assessed PFS: The time from randomization to PD or death from any cause, whichever occurs first.

Secondary endpoints 8

1. Key secondary endpoint: Investigator-assessed PFS: The time from randomization to PD or death from any cause, whichever occurs first.
2. Other secondary endpoints: OS: The time from randomization to death.
3. IRC- and investigator-assessed ORR: ORR includes complete response (CR), complete response with incomplete bone marrow recovery (CRi) or partial response (PR). CLL responsewill be assessed according to IWCLL NCI-WG guidelines (2018 Edition), and SLL response will be assessed according to Lugano 2014 criteria for response assessment in lymphoma.
4. IRC- and investigator-assessed TTR: The interval from randomization to the date of the first confirmed CR, CRi, or PR.
5. IRC- and investigator-assessed DOR: The interval from the date of first confirmed CR, CRi or PR to PD, or the start of a new anti-tumor treatment, or death, whichever occurs first.
6. MRD negativity rate: Proportion of patients with MRD-negative result in bone marrow, peripheral blood, either or both.
7. Safety and tolerability of patients: Treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) will be evaluated.
8. Concentration data of Lisaftoclax and critical parameters of population pharmacokinetics.

Investigational products

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

Test 3

Comparator 6

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,CMO

Public contact point

Organisation

Ascentage Pharma Group Inc.

Contact name

Yifan Zhai,CMO

Third parties 12

Locations

3 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 59 files

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

Application history

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