APG-2575 for CLL

Recruiting at 8 trial locations

Overseen By Laura Glass

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ascentage Pharma Group Inc.

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: HIV, Hepatitis B, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

144 Participants Needed

Trial Summary

What is the purpose of this trial?

Assess the safety and tolerability, identify dose-limiting toxicities (DLT) and determine the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) of lisaftoclax.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain medications like strong CYP3A inhibitors or inducers within 7 days before starting the trial.

What data supports the effectiveness of the drug APG-2575 (Lisaftoclax) for treating chronic lymphocytic leukemia (CLL)?

Venetoclax, a drug similar to APG-2575, has shown effectiveness in treating CLL, especially in patients with high-risk features, by achieving significant remission rates and being generally well-tolerated. This suggests that APG-2575, which may work in a similar way, could also be effective for CLL. ^{1 2 3 4 5}

Research Team

Yifan Zhai, MD, PhD

Principal Investigator

Ascentage Pharma Group Inc.

Eligibility Criteria

This trial is for adults over 18 with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who have tried at least one treatment without success and need more therapy. They should be relatively active (ECOG ≤2), show signs of disease progression, and meet specific blood count and organ function criteria.

Inclusion Criteria

I can take care of myself and am up and about more than 50% of my waking hours.

My platelet count is high enough without needing a transfusion in the past week.

Females of childbearing potential and non-sterile males must practice at least one of the following methods of birth control with partner(s) throughout the study and for 90 days after discontinuing study drug: Total abstinence from sexual intercourse, Surgically sterile partner(s), Intrauterine device (IUD), Double-barrier method, Hormonal contraceptives for at least 3 months prior to study drug administration, Male patients must refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug, Ability to understand and willingness to sign a written informed consent form, Willingness and ability to comply with study procedures and follow-up examination

Exclusion Criteria

Any other condition or circumstance that would make the patient unsuitable for participation in the study

I have not had radiation therapy in the last 14 days.

I have an active hepatitis B or C infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ramp-up

Participants undergo a ramp-up period with APG-2575 starting at 20 mg and increasing to a maximum of 1200 mg over several days

3-9 days

Dose Escalation and Expansion

APG-2575 is studied at different dose levels as monotherapy and in combination with other agents using a 3+3 dose escalation design, followed by dose expansion at RP2D

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• APG2575

Trial Overview The study tests APG-2575 alone or with other treatments to find the safest dose that's still effective for CLL/SLL. It aims to identify any toxic effects at different doses and establish a recommended dosage for future phase 2 trials.

Participant Groups

Group I: Lisaftoclax 800mg Experimental Treatment 1 Intervention

Lisaftoclax 800mg ramp up

Group II: Lisaftoclax 600mg Experimental Treatment 1 Intervention

Lisaftoclax 600mg ramp up

Group III: Lisaftoclax 400mg Experimental Treatment 1 Intervention

Lisaftoclax 400mg ramp up

Group IV: Lisaftoclax 1000mg Experimental Treatment 1 Intervention

Lisaftoclax 1,000mg ramp up

APG2575 is already approved in China for the following indications:

Approved in China as Lisaftoclax for:

• Relapsed/refractory chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)

Who Is Running the Clinical Trial?

Ascentage Pharma Group Inc.

Lead Sponsor

Trials

54

Recruited

5,700+

Findings from Research

Venetoclax, an oral BCL-2 inhibitor, is an effective long-term treatment for patients with relapsed/refractory chronic lymphocytic leukemia (CLL), particularly those with high-risk features like chromosome 17p deletion, based on a safety analysis of 350 patients.

The treatment is generally well tolerated, with manageable side effects; however, common adverse events included diarrhea (41%), neutropenia (40%), and nausea (39%), and serious infections occurred in 15% of patients, indicating the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia. Davids, MS., Hallek, M., Wierda, W., et al.[2019]

A middle-aged female patient with poor prognosis unmutated IGHV chronic lymphocytic leukemia (CLL) achieved complete cytogenetic and molecular remission after six cycles of low-dose recombinant human IL-2 combined with low-dose venetoclax, indicating the treatment's efficacy.

The combination therapy of low-dose rIL-2 and venetoclax is a non-toxic immunotherapy that stimulates natural killer cells, making it a promising outpatient treatment option for patients with poor prognosis CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Remission Using Low-Dose Immunotherapy with Minimal Toxicities for Poor Prognosis IGHV- Unmutated Chronic Lymphocytic Leukemia. Maharaj, D., Srinivasan, G., Abreu, MM., et al.[2021]

The German CLL Study Group is focusing on developing optimal, non-toxic drug combinations for chronic lymphocytic leukemia (CLL) therapy, utilizing novel agents like bendamustine, idelalisib, and ibrutinib.

Phase II combination trials (BXX series) are underway to evaluate the effectiveness of these combinations, aiming to improve treatment outcomes for CLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current strategies to create tailored and risk-adapted therapies for CLL patients. Cramer, P., Eichhorst, B., Reinhardt, HC., et al.[2021]

Venetoclax is an effective treatment for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) with the 17p deletion, showing strong activity both as a standalone therapy and in combination with other treatments.

The drug is notable for inducing deep and durable complete remissions, although it carries a manageable toxicity profile, including risks of hematologic side effects and tumor lysis syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCL-2 as a therapeutic target in chronic lymphocytic leukemia. Daniel, C., Mato, AR.[2017]

In a phase 2 study of 36 patients with chronic lymphocytic leukemia (CLL) who had previously been treated with idelalisib, venetoclax showed a promising objective response rate of 67%, indicating its efficacy in patients whose disease was refractory to prior B-cell receptor inhibitors.

Venetoclax was well-tolerated, with the most common adverse events being neutropenia and diarrhea, but no cases of tumor lysis syndrome were reported, suggesting a favorable safety profile for this treatment in heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy. Coutre, S., Choi, M., Furman, RR., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular Remission Using Low-Dose Immunotherapy with Minimal Toxicities for Poor Prognosis IGHV- Unmutated Chronic Lymphocytic Leukemia. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Current strategies to create tailored and risk-adapted therapies for CLL patients. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

BCL-2 as a therapeutic target in chronic lymphocytic leukemia. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy. [2021]