AK117 + Azacitidine for Myelodysplastic Syndrome

Recruiting at 16 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new treatment, AK117 (also known as Ligufalimab), combined with azacitidine for individuals with higher-risk myelodysplastic syndromes (HR-MDS), a type of blood disorder. Participants will be randomly assigned to receive either AK117 at one of two doses or a placebo, both in combination with azacitidine. The goal is to determine if AK117 improves symptoms and safety compared to the placebo. The trial seeks individuals newly diagnosed with HR-MDS who can undergo blood and bone marrow tests. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

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.

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

Research has shown that combining AK117 and azacitidine is generally safe for people. Studies have found that this treatment has a manageable safety profile, meaning most people do not experience serious side effects. Anemia, a common issue involving fewer red blood cells than normal, occurs only at a low rate. Overall, the treatment is well-tolerated, with most people handling it without major problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myelodysplastic syndrome?

Researchers are excited about AK117 for treating myelodysplastic syndrome because it offers a potentially new approach by targeting the CD47-SIRPα pathway, which is different from the standard treatments like azacitidine alone. AK117 is an antibody designed to block CD47, a protein that cancer cells use to evade the immune system, allowing the body's defenses to better recognize and attack the cancer. Unlike traditional treatments that primarily focus on altering the bone marrow environment, AK117 directly enhances the immune response against the cancer cells, which could lead to more effective outcomes. Additionally, it is administered intravenously, which might improve its absorption compared to oral medications.

What evidence suggests that this trial's treatments could be effective for higher-risk myelodysplastic syndromes?

This trial will evaluate AK117 combined with azacitidine for treating higher-risk myelodysplastic syndromes (HR-MDS). Studies have shown that this combination looks promising. Specifically, previous research indicated that 55% of patients who received these drugs experienced a complete response, significantly improving their condition. Among them, 45% achieved complete remission, showing no signs of the disease. The treatment was generally well-tolerated, with fewer cases of anemia (low red blood cell count) than expected. These findings suggest that AK117 combined with azacitidine could be a strong option for people with HR-MDS. Participants in this trial may receive different doses of AK117 or a placebo, all in combination with azacitidine. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 (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]

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]

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]

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 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]

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]

Citations

1. akesobio.com akesobio.com/en/media/akeso-news/231214/

Akeso Published Results from CD47 Antibody Ligufalimab ... The combination of AK117 and AZA exhibited a manageable safety profile with a low incidence of anemia, and demonstrated promising efficacy as a ...

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1865/504435/AK117-anti-CD47-monoclonal-antibody-in-Combination

AK117 (anti-CD47 monoclonal antibody) in Combination with ... AK117 in combination with AZA was well tolerated with low incidence of anemia and demonstrated promising efficacy in patients with newly diagnosed HR-MDS.

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4280/503787/A-Phase-1b-Study-Evaluating-the-Safety-and

A Phase 1b Study Evaluating the Safety and Efficacy of AK117 ... Out of 20 evaluable patients, 11 (55%) achieved a CCR, including 9 (45%) with a CR and 2 (10%) with a CRi. Stable disease (SD) was reported in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04900350

NCT04900350 | A Trial of AK117 (Anti-CD47) in Patients ... The purpose of this study is to evaluate the safety and efficacy of AK117 + azacitidine in subjects with higher-risk MDS. Official Title. A Phase I/II Trial ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123084689

AK117 (anti-CD47 monoclonal antibody) in Combination ... AK117 in combination with AZA was well tolerated with low incidence of anemia and demonstrated promising efficacy in patients with newly diagnosed HR-MDS.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06196203

NCT06196203 | A Study of AK117 in Combination With ... This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of AK117 or placebo, combined with ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123084689

AK117 (anti-CD47 monoclonal antibody) in Combination ... AK117 in combination with AZA was well tolerated with low incidence of anemia and demonstrated promising efficacy in patients with newly diagnosed HR-MDS.