AK117 + Azacitidine for Myelodysplastic Syndrome

Recruiting at 14 trial locations

Overseen By Wenting Li, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Akeso

Must be taking: Azacitidine

Must not be taking: CD47 agents

Disqualifiers: Hypertension, Cardiopulmonary disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 2 years

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have high blood pressure, it should be controlled with oral medication before joining the study.

What data supports the effectiveness of the drug AK117 + Azacitidine for Myelodysplastic Syndrome?

Azacitidine has been shown to be effective in treating higher-risk myelodysplastic syndromes (MDS) by significantly prolonging survival and delaying progression to acute leukemia, as demonstrated in large clinical trials. While there is no direct data on AK117, similar treatments combining azacitidine with other immune therapies have shown promising results in related conditions. ^{1 2 3 4 5}

Is the combination of AK117 (Ligufalimab) and Azacitidine safe for treating Myelodysplastic Syndrome?

There is no specific safety data available for the combination of AK117 (Ligufalimab) and Azacitidine in treating Myelodysplastic Syndrome. However, Azacitidine alone has been shown to be safe and effective in treating Myelodysplastic Syndromes in community practice, with consistent safety and tolerability. ^{3 4 5 6 7}

What makes the drug AK117 + Azacitidine unique for treating myelodysplastic syndrome?

AK117 (Ligufalimab) is a novel drug that, when combined with azacitidine, may offer a new approach to treating myelodysplastic syndrome by potentially enhancing the immune response against cancer cells, which is different from the standard use of azacitidine alone or in combination with other drugs like lenalidomide. ^{2 3 4 8 9}

What is the purpose of this trial?

This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of AK117 or placebo, combined with azacitidine in patients with newly diagnosed higher-risk myelodysplastic syndromes (HR-MDS).

Eligibility Criteria

This trial is for adults over 18 with newly diagnosed high-risk myelodysplastic syndromes (HR-MDS) and less than 20% bone marrow or blood blasts. Participants need an ECOG score of 0-2, indicating they can perform daily activities, and must expect to live at least three more months. Women of childbearing age must test negative for pregnancy and use contraception, as should men with partners who could become pregnant.

Inclusion Criteria

Suitable venous access for the study-required blood sampling (i.e., including PK and immunogenicity)

Unsterilized male patients having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until 180 days after the last dose of study treatment

Expected life expectancy ≥ 3 months

Exclusion Criteria

Concurrently participating in another interventional clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study

Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies

Patients who are breastfeeding or plans to breastfeed during the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AK117 or placebo in combination with azacitidine. AK117 is administered intravenously, and azacitidine is administered subcutaneously (75 mg/m2, D1-7, Q4W).

Up to approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of overall survival, time to response, and adverse events.

Up to approximately 2 years

Treatment Details

Interventions

• AK117

Trial Overview The study tests AK117 combined with Azacitidine versus a placebo plus Azacitidine in patients with HR-MDS. It's a Phase 2 trial where participants are randomly assigned to either the treatment group or the control group without knowing which one they're in (double-blind). The goal is to assess how well AK117 works and its safety when given alongside Azacitidine.

Participant Groups

Group I: AK117 (dose 2) in combination with azacitidine Experimental Treatment 2 Interventions

Subjects receive AK117 (dose 2) intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously

Group II: AK117 (dose 1) in combination with azacitidine Experimental Treatment 2 Interventions

Subjects receive AK117 (dose 1) intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously

Group III: Placebo in combination with azacitidine Placebo Group 2 Interventions

Subjects receive placebo intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously

AK117 is already approved in China for the following indications:

Approved in China as Ligufalimab for:

• Acute Myeloid Leukemia (AML)

Who Is Running the Clinical Trial?

Akeso

Lead Sponsor

Trials

122

Recruited

23,400+

Dr. Simon Williams

Akeso

Chief Executive Officer since 2022

PhD in Organic Chemistry from Cambridge University

Dr. Baiyong Li

Akeso

Chief Medical Officer

MD from an unspecified institution

Findings from Research

In the AZA-001 trial, azacitidine significantly improved survival in patients with high-risk myelodysplastic syndrome and acute myeloid leukemia, with 91 out of 179 patients responding to treatment after a median of 14 cycles.

Continued treatment with azacitidine beyond the first response led to an improved response category in 48% of patients, suggesting that ongoing therapy can enhance clinical benefits for those who initially respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes. Silverman, LR., Fenaux, P., Mufti, GJ., et al.[2022]

Azacitidine has been shown to significantly prolong the time to progression to acute myeloid leukemia or death in myelodysplastic syndromes (MDS) patients, with a median time of 21 months compared to 13 months for supportive care in a study of 191 patients.

In a larger trial with 358 patients, azacitidine also significantly improved overall survival, extending it to 24.5 months compared to 15.0 months with conventional care, establishing it as a key first-line treatment for higher-risk MDS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of azacitidine trials in Intermediate-2-and High-risk myelodysplastic syndromes. Fenaux, P., Ades, L.[2022]

In a phase II trial involving 160 patients with higher risk myelodysplastic syndromes and related conditions, the combination of azacitidine and lenalidomide did not show improved clinical benefits or survival rates compared to azacitidine alone.

Both treatment groups experienced similar rates of adverse events and maintained good adherence to the treatment protocol, indicating that while the combination therapy was tolerable, it did not enhance efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine with or without lenalidomide in higher risk myelodysplastic syndrome & low blast acute myeloid leukemia. Kenealy, M., Hertzberg, M., Benson, W., et al.[2020]

In a trial involving 70 patients with relapsed/refractory acute myeloid leukemia (AML), the combination of azacitidine and nivolumab resulted in an overall response rate of 33%, with particularly promising results in patients who had not previously received hypomethylating agents, achieving a response rate of 58%.

The treatment was generally safe, with only 11% of patients experiencing grade 3 to 4 immune-related adverse events, and pretherapy levels of CD3 and CD8 in bone marrow and blood were identified as potential biomarkers for predicting patient response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Biomarkers of Response to Azacitidine and Nivolumab in Relapsed/Refractory Acute Myeloid Leukemia: A Nonrandomized, Open-Label, Phase II Study. Daver, N., Garcia-Manero, G., Basu, S., et al.[2020]

In a phase II trial involving 37 patients with myelodysplastic syndromes (MDS), the combination of azacitidine and pembrolizumab showed a high overall response rate of 76% in previously untreated patients, indicating promising efficacy.

The treatment was found to be safe with manageable toxicities, including pneumonia and immune-related adverse events, suggesting that this combination therapy warrants further investigation in earlier treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of azacitidine with pembrolizumab in patients with intermediate-1 or higher-risk myelodysplastic syndrome. Chien, KS., Kim, K., Nogueras-Gonzalez, GM., et al.[2021]

In a phase 1b study involving 46 patients with relapsed/refractory or HMA-naïve myelodysplastic syndrome, atezolizumab alone or in combination with azacitidine showed a high early death rate, with 61.9% of patients in cohort C experiencing death, raising safety concerns.

The study found poor efficacy, with no responses in cohort A and only 14.3% response in cohort B, leading to the conclusion that the risk-benefit profile for atezolizumab in these patient populations is unfavorable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome. Gerds, AT., Scott, BL., Greenberg, P., et al.[2022]

The AVIDA registry, which included 421 patients with myelodysplastic syndromes (MDS) across 105 US sites, demonstrated that azacitidine is effective in achieving hematologic improvement and transfusion independence, regardless of the administration route or dosing schedule.

The safety and tolerability of azacitidine were consistent with previous studies, confirming its effectiveness and safety for both lower- and higher-risk MDS patients in community practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with myelodysplastic syndromes treated with azacitidine in clinical practice: the AVIDA registry. Grinblatt, DL., Sekeres, MA., Komrokji, RS., et al.[2019]

Azacitidine (AZA) is the standard frontline treatment for higher-risk myelodysplastic syndrome (MDS) and has been shown to significantly improve overall survival compared to conventional care in a phase III trial.

There is a need for further research to identify better prognostic factors for response to AZA and to explore combination therapies with other effective drugs to enhance treatment outcomes for patients with MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of advanced myelodysplastic syndrome with demethylating agents: azacitidine. Adès, L., Itzykson, R., Fenaux, P.[2013]

The combination therapy of lenalidomide and azacitidine showed a high overall response rate of 72% in patients with higher-risk myelodysplastic syndromes (MDS), with 44% achieving a complete response and a median duration of complete response lasting over 17 months.

This treatment was well-tolerated, although some patients experienced significant adverse events, such as febrile neutropenia in 22% of cases, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes. Sekeres, MA., Tiu, RV., Komrokji, R., et al.[2021]

References

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

Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Review of azacitidine trials in Intermediate-2-and High-risk myelodysplastic syndromes. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Azacitidine with or without lenalidomide in higher risk myelodysplastic syndrome & low blast acute myeloid leukemia. [2020]

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

Efficacy, Safety, and Biomarkers of Response to Azacitidine and Nivolumab in Relapsed/Refractory Acute Myeloid Leukemia: A Nonrandomized, Open-Label, Phase II Study. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Phase II study of azacitidine with pembrolizumab in patients with intermediate-1 or higher-risk myelodysplastic syndrome. [2021]

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

Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome. [2022]

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

Patients with myelodysplastic syndromes treated with azacitidine in clinical practice: the AVIDA registry. [2019]

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

Treatment of advanced myelodysplastic syndrome with demethylating agents: azacitidine. [2013]

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

Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes. [2021]