Lisaftoclax + Azacitidine for Myelodysplastic Syndrome

Recruiting at 1 trial location

Overseen By Qian Niu, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ascentage Pharma Group Inc.

Must not be taking: CYP3A4 inducers, inhibitors

Disqualifiers: Other malignancies, Stem cell transplant, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

490 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with higher-risk myelodysplastic syndrome (HR-MDS), a condition where blood cells fail to mature properly. The study compares the combination of two drugs, Lisaftoclax (a potential new drug) and azacitidine, against azacitidine with a placebo (an inactive substance). The researchers aim to determine if the new drug combination extends patient survival. Individuals recently diagnosed with HR-MDS who can manage daily activities well might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain drugs that affect liver enzymes (CYP3A4) within 7 days before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have generally found the combination of lisaftoclax and azacitidine to be well-tolerated by patients. Research shows that most side effects from these drugs can be managed. For instance, one study found that patients experienced side effects like low blood cell counts, common in treatments for blood disorders. However, these effects were usually mild to moderate and could be handled with standard medical care.

Lisaftoclax, whether used alone or with azacitidine, has shown promising safety results in patients with similar conditions. While some side effects might occur, they are not severe and can be managed effectively. Overall, the combination treatment appears to have a good safety profile based on the available data. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for myelodysplastic syndrome (MDS) focus on therapies like azacitidine, which tries to alter abnormal blood cell production. But Lisaftoclax (APG-2575), when combined with azacitidine, brings something new to the table. Lisaftoclax takes a unique approach by targeting and inhibiting a protein known as BCL-2, which helps cancer cells survive. This mechanism is exciting because it directly induces cancer cell death, potentially enhancing treatment effectiveness. Researchers are hopeful that this combination can improve outcomes for MDS patients, making it a promising development in the fight against this condition.

What evidence suggests that Lisaftoclax combined with Azacitidine could be an effective treatment for Myelodysplastic Syndrome?

This trial will compare the combination of Lisaftoclax and Azacitidine with a placebo combined with Azacitidine for treating higher-risk myelodysplastic syndrome (HR-MDS). Research has shown that combining Lisaftoclax and Azacitidine may help treat HR-MDS. Previous studies found that this combination can extend patients' lives. The treatment blocks a protein called BCL-2, which cancer cells need to survive. Early results suggest that this combination is generally safe and doesn't cause severe side effects for most patients. Overall, the evidence supports its potential to improve outcomes for those with HR-MDS. ^{1 2 3 6 7}

Who Is on the Research Team?

Xiaojun Huang, M.D., Ph.D.

Principal Investigator

Peking University People's Hospital

Guillermo Garcia-Manero, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for newly diagnosed patients with higher-risk Myelodysplastic Syndrome (HR-MDS), a condition that can lead to leukemia. Specific eligibility details are not provided, but typically participants must meet certain health standards and may be excluded based on other medical conditions or treatments.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My organs are functioning well.

I have been recently diagnosed with a high-risk form of MDS.

Exclusion Criteria

I do not have any ongoing infections that aren't under control.

I haven't taken strong drugs that affect liver enzymes in the last week.

Any condition that the subject is deemed inappropriate for study participation after evaluation by the investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lisaftoclax (APG-2575) combined with azacitidine or placebo combined with azacitidine

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Lisaftoclax (APG-2575)

Trial Overview The study is testing the effectiveness of Lisaftoclax (APG-2575) combined with Azacitidine (AZA) compared to a placebo combined with AZA in improving overall survival rates in HR-MDS patients. It's a phase III trial, meaning it's late-stage research involving more participants to confirm effectiveness and monitor side effects.

How Is the Trial Designed?

Group I: Lisaftoclax (APG-2575) combined with Azacitidine Experimental Treatment 2 Interventions

Group II: Placebo combined with Azacitidine Active Control 2 Interventions

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Ascentage Pharma Group Inc.

Lead Sponsor

Trials

54

Recruited

5,700+

Published Research Related to This Trial

In a phase II study involving 60 older or unfit patients with newly diagnosed acute myeloid leukemia (AML), the combination of venetoclax with cladribine and low-dose cytarabine alternating with venetoclax and 5-azacitidine resulted in a high composite complete response rate of 93%.

The treatment showed promising overall survival and disease-free survival rates, with only one death occurring within 4 weeks, indicating that this regimen is effective and has a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. Kadia, TM., Reville, PK., Wang, X., et al.[2023]

In a study involving 21 patients with Myelodysplastic Syndromes (MDS) and secondary Acute Myeloid Leukemia (sAML), the combination of venetoclax and azacitidine (5-AZA) was shown to effectively target malignant cells even after failure of hypomethylating agents (HMA).

Importantly, this combination therapy demonstrated the ability to spare healthy hematopoiesis, which is crucial for maintaining blood cell production and reducing toxicity in elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax with azacitidine targets refractory MDS but spares healthy hematopoiesis at tailored dose. Jilg, S., Hauch, RT., Kauschinger, J., et al.[2020]

In a phase 1b study involving 44 patients with relapsed/refractory higher-risk myelodysplastic syndromes (MDS), the combination of venetoclax and azacitidine demonstrated significant activity, with a median overall survival of 12.6 months after prior treatment failure with hypomethylating agents.

The treatment resulted in hematological improvements, including complete remission in 7% of patients and transfusion independence in 36%, indicating that venetoclax plus azacitidine can provide meaningful clinical benefits for patients with limited options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. Zeidan, AM., Borate, U., Pollyea, DA., et al.[2023]

The Vidaza Access Program in Belgium successfully facilitated access to azacitidine treatment for 175 patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) by streamlining the approval process for patient dossiers.

Out of the 175 patient dossiers submitted, 163 were approved by Celgene, demonstrating the program's effectiveness in ensuring timely treatment initiation without financial risk to hospitals, which is crucial for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. Meers, S., Selleslag, D., Potier, H., et al.[2018]

In a study of 50 adults with acute myeloid leukemia (AML) in Mexico and Peru, venetoclax-based therapy showed a high complete response rate of 78.6% in newly diagnosed patients and 45.5% in those with relapsed/refractory disease, indicating its efficacy in treating AML.

The median overall survival was 9.6 months for newly diagnosed patients and 8 months for relapsed/refractory patients, suggesting that venetoclax is a viable treatment option even in real-world settings, despite common hematologic toxicities and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. Gómez-De León, A., Demichelis-Gómez, R., Pinedo-Rodríguez, A., et al.[2022]

In a phase 1/2 study involving six Japanese patients aged 60 and older with acute myeloid leukaemia, the combination of venetoclax and azacitidine demonstrated a high response rate, with 83% of patients achieving a response, including three complete remissions.

The treatment was generally well tolerated, with a median overall survival of 15.7 months, although some patients experienced serious adverse events, including grade 3 fungal pneumonia, which required treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. Taniguchi, S., Yamauchi, T., Choi, I., et al.[2021]

The combination of azacitidine and venetoclax is safe and well-tolerated in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia, with a recommended phase 2 dose established as azacitidine 75 mg/m2 for 5 days plus venetoclax 400 mg for 14 days.

The treatment showed a high overall response rate of 87% among the 23 enrolled patients, indicating promising preliminary activity for this combination therapy in treatment-naive and relapsed or refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine plus venetoclax in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1-2 study. Bazinet, A., Darbaniyan, F., Jabbour, E., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3202/529924/Lisaftoclax-APG-2575-a-Novel-BCL-2-Inhibitor-in

Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor, in ... We present follow-up safety and efficacy data from a phase 1b/2 clinical trial evaluating lisaftoclax combined with azacitidine in adults (≥ 18 years) with MDS.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06641414

Study Details | NCT06641414 | Lisaftoclax (APG-2575) ... 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 ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6505

Phase 1b/2 study of lisaftoclax (APG-2575) combined with ... LISA at different dose regimens combined with AZA provides promising treatment options for pts with HR-MDS or AML. No DLTs occurred. The MTD was not reached.

4. ascentage.com ascentage.com/ascentage-pharma-announces-global-registrational-phase-iii-study-of-lisaftoclax-for-first-line-treatment-of-patients-with-higher-risk-myelodysplastic-syndrome-cleared-by-us-fda-and-ema/

Press Releases Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor, in Combination with Azacitidine in Treatment of Patients with Myelodysplastic Syndrome (MDS).

5. targetedonc.com targetedonc.com/view/global-phase-3-trial-of-lisaftoclax-cleared-for-higher-risk-mds

Global Phase 3 Trial of Lisaftoclax Cleared for Higher-Risk ... Interim results have shown encouraging efficacy and a manageable safety profile for the lisaftoclax and azacitidine combination. The ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123095277

Safety and Efficacy of Lisaftoclax (APG-2575), a Novel ... Lisaftoclax showed favorable tolerability as monotherapy and when combined with AZA or HHT, exhibiting encouraging clinical efficacy among pts with R/R AML or ...

7. onclive.com onclive.com/view/lisaftoclax-plus-azacitidine-shows-clinical-activity-and-manageable-safety-in-higher-risk-mds

Lisaftoclax Plus Azacitidine Shows Clinical Activity and ... Lisaftoclax combined with azacitidine showed significant efficacy in higher-risk MDS, with a 73.9% ORR in treatment-naive patients and 75.0% in ...