Evorpacept + Azacitidine for Myelodysplastic Syndrome

No longer recruiting at 23 trial locations

Overseen By Abraham Fong, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ALX Oncology Inc.

Must not be taking: Anti-CD47, Anti-SIRPα

Disqualifiers: Allo-HSCT, Viral infections, others

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

Compensation: Varies

Number of Visits: 14

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new drug combination for individuals with higher-risk myelodysplastic syndrome (MDS), a blood disorder where bone marrow doesn't produce enough healthy blood cells. Researchers aim to determine if evorpacept (an experimental treatment), combined with azacitidine, is safe and effective for this condition. The study consists of two parts: one where participants receive both drugs and another where they receive azacitidine alone for comparison. Individuals diagnosed with higher-risk MDS, who have not undergone certain previous treatments, and whose condition impacts their daily life might be suitable for the trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that evorpacept, when combined with azacitidine, is generally well-tolerated by patients with myelodysplastic syndrome (MDS). Studies have found that this combination has a safety profile similar to azacitidine alone, which reassures those considering this treatment. Azacitidine is a well-known drug for treating MDS, but some side effects have been reported.

In earlier research, most side effects of azacitidine were serious, and a small number of cases resulted in death. However, many patients lived longer with its use. The combination of evorpacept and azacitidine appears safe and initially effective, offering new hope for patients with higher-risk MDS. Patients should always consult healthcare professionals to understand the potential risks and benefits before joining clinical trials. ^{1 2 3 4 5}

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

Researchers are excited about evorpacept, especially when paired with azacitidine, because it offers a novel approach to treating myelodysplastic syndrome (MDS). Most current treatments for MDS focus on modifying blood cell production, but evorpacept works differently by enhancing the immune system's ability to target and destroy cancer cells. This is achieved through its action as a CD47 blocker, which helps the immune system recognize and attack cancer cells more effectively. By combining evorpacept with azacitidine, there’s potential to improve patient outcomes beyond what azacitidine alone can offer, making this combination a promising development in MDS therapy.

What evidence suggests that this trial's treatments could be effective for myelodysplastic syndrome?

Research has shown that evorpacept, when combined with azacitidine, offers promising early results in treating myelodysplastic syndrome (MDS). In this trial, one group of participants will receive both evorpacept and azacitidine. Evorpacept blocks CD47, a protein that cancer cells use to evade the immune system. Earlier studies found this combination well-tolerated, with a safety profile similar to azacitidine alone. Patients receiving both treatments demonstrated early signs of effectiveness, providing hope for those with higher-risk MDS. This combination presents an encouraging option for patients seeking new treatment possibilities. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults over 18 with higher risk Myelodysplastic Syndrome (MDS) that is either untreated or has come back after treatment can join this study. They must have good kidney and liver function, and be physically able to participate. People who've had certain previous treatments or stem cell transplants, or active viral infections like hepatitis B/C, HIV/AIDS, or COVID-19 cannot take part.

Inclusion Criteria

I have a high-risk type of MDS that hasn't been treated yet.

My kidney and liver are working well.

I have a high-risk type of MDS that is either new or has come back.

Exclusion Criteria

I do not have active hepatitis B or C, HIV/AIDS, or COVID-19.

I have never been treated with anti-CD47 or anti-SIRPα medications.

I had a stem cell transplant for my blood cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Dose escalation of evorpacept (ALX148) in combination with azacitidine to evaluate safety and tolerability

Approximately 2 years

7 days of a 28-day cycle

Phase 2 Treatment

Evaluation of the efficacy of evorpacept (ALX148) in combination with azacitidine compared to azacitidine alone

Approximately 6 months

7 days of a 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Evorpacept

Trial Overview The trial is testing a combination of two drugs: Evorpacept (ALX148) and Azacitidine in patients with high-risk MDS. It's designed in two phases; the first phase includes those previously treated for MDS while the second focuses on those who haven't been treated before.

How Is the Trial Designed?

Group I: evorpacept (ALX148) + azacitidine Experimental Treatment 2 Interventions

Phase 1: Participants will receive escalating doses of evorpacept (ALX148) in combination with azacitidine 75 mg/m2 IV or subcutaneous daily for 7 days of a 28 day cycle Phase 2: Participants will receive evorpacept (ALX148) at the recommended Phase 2 dose in combination with azacitidine 75 mg/m2 IV or subcutaneous daily for 7 days of a 28-day cycle

Group II: azacitidine Active Control 1 Intervention

Phase 2 only: Participants will receive azacitidine 75 mg/m2 IV or subcutaneous daily for 7 days of a 28-day cycle

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?

ALX Oncology Inc.

Lead Sponsor

Trials

9

Recruited

1,200+

Published Research Related to This Trial

Azacitidine is an effective and well-tolerated treatment for patients with higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), including older patients who are ineligible for stem cell transplants, as demonstrated in pivotal phase 3 trials.

It is the only approved hypomethylating agent that has been shown to prolong overall survival compared to conventional care, making it the recommended first-line treatment for most patients with higher-risk MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine: A Review in Myelodysplastic Syndromes and Acute Myeloid Leukaemia. Scott, LJ.[2022]

In a real-life study of 49 patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), azacitidine demonstrated a clinically acceptable safety profile, with 67.3% of patients experiencing treatment-related adverse events.

Efficacy results showed that 41.4% of MDS and CMML patients achieved a complete or partial response, and 43.8% of transfusion-dependent patients became transfusion-independent, with a median overall survival of 490 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey. Beguin, Y., Selleslag, D., Meers, S., et al.[2015]

In a study of 24 patients with higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), the combination of 5-azacytidine (AZA) and valproate (VPA) resulted in a 37% overall response rate, with a notably higher response of 57% in previously untreated patients, particularly those with MDS (64%).

The treatment led to complete remission (CR) in 29% of patients, with some achieving complete cytogenetic remission, indicating that VPA may enhance the efficacy of AZA, although further randomized trials are needed to confirm the role of HDAC inhibitors in this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of poor-risk myelodysplastic syndromes and acute myeloid leukemia with a combination of 5-azacytidine and valproic acid. Kuendgen, A., Bug, G., Ottmann, OG., et al.[2021]

In a study involving 277 patients with higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML), azacitidine combined with lenalidomide showed a higher overall response rate (ORR) of 68% in CMML patients compared to 28% for azacitidine alone, indicating a potential benefit for this specific group.

Overall, the combination therapies (azacitidine plus lenalidomide and azacitidine plus vorinostat) did not significantly outperform azacitidine monotherapy in terms of ORR, suggesting that while combinations may be beneficial for certain patients, they may also be impacted by dose modifications and other factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Study of Azacitidine Alone or in Combination With Lenalidomide or With Vorinostat in Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia: North American Intergroup Study SWOG S1117. Sekeres, MA., Othus, M., List, AF., et al.[2022]

In a study of 149 patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML), azacitidine treatment resulted in a median progression-free survival (PFS) of 10.9 months and an overall survival (OS) of 14.1 months, demonstrating its effectiveness in a real-world clinical setting.

The safety profile of azacitidine was consistent with previous clinical trials, and factors such as Eastern Cooperative Oncology Group (ECOG) performance status and red blood cell transfusion prior to treatment were identified as predictive factors for better PFS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study). Wehmeyer, J., Zaiss, M., Losem, C., et al.[2019]

Azacitidine significantly improves overall survival in patients with myelodysplastic syndromes and related disorders, with a median survival of 24.5 months compared to 15 months for conventional care, based on a trial of 358 patients.

While azacitidine offers a viable treatment option when stem cell transplantation is not possible, it carries risks of severe toxicity and other side effects, highlighting the need for careful patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine. Poor-prognosis myelodysplasia: promising, but more data needed. [2013]

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]

5-azacytidine (5-AZA) has shown clinical and hematological improvement in elderly patients with high-risk myelodysplastic syndromes (MDS), based on the treatment of three case studies.

The use of 5-AZA is associated with acceptable side effects, making it a promising therapeutic option for managing high-risk MDS in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacytidine for the treatment of myelodysplastic syndromes in the elderly. Diez Campelo, M., Delgado, RG., Molias, AC., et al.[2014]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121045468

Evorpacept (ALX148), a CD47-Blocking Myeloid ... The myeloid checkpoint inhibitor evorpacept was well tolerated in combination with AZA with an initial safety profile similar to that of AZA monotherapy.

2. alxoncology.com alxoncology.com/wp-content/uploads/2021/12/ALX-ASH-ASPEN-02-Poster-Dec21.pdf

Evorpacept (ALX148), a CD47-Blocking Myeloid ... demonstrate the safety of combining evorpacept with azacitidine and promising initial activity in patients with myelodysplastic syndrome (MDS). Figure 1.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04417517

A Study of Evorpacept (ALX148) With Azacitidine for ... This Phase 1/2 clinical study will evaluate evorpacept (ALX148) in combination with azacitidine for the treatment of patients with higher risk myelodysplastic ...

4. researchgate.net researchgate.net/publication/356496882_Evorpacept_ALX148_a_CD47-Blocking_Myeloid_Checkpoint_Inhibitor_in_Combination_with_Azacitidine_A_Phase_1_2_Study_in_Patients_with_Myelodysplastic_Syndrome_ASPEN-02

Evorpacept (ALX148), a CD47-Blocking Myeloid ... Here, we present results from the phase 1 part of the ASPEN-02 study evaluating the safety and tolerability of evorpacept administered in ...

5. healthtree.org healthtree.org/mds/community/articles/evorpacept-and-azacitidine-high-risk-mds

Study of Evorpacept and Azacitidine for High-Risk MDS Discover Evorparcept's potential in high-risk MDS: ASPEN-02 study insights, safety, and treatment efficacy for patients seeking new options.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2948932/

Safety and efficacy of azacitidine in myelodysplastic ... Azacitidine has been reported to prolong survival in MDS patients. Azacitidine has been studied in different dosing schedules and combination therapies with the ...

7. hematologyadvisor.com hematologyadvisor.com/news/azacitidine-myelodysplastic-syndrome-mds-adverse-events-safety-concerns/

New Adverse Events Highlight Safety Concerns With ... Most AEs (95.78%) were classified as serious, and 40.87% resulted in death. Health professionals submitted nearly 90% of the reports, with the ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2817034/

5-azacitidine prolongs overall survival in patients with ... Patients with intermediate-2 and high-risk myelodysplastic syndrome (MDS) have a survival rate of 0.4 to 1.2 years as well as a high risk of their disease ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6509

Preliminary safety and efficacy of oral azacitidine (Oral-AZA ... Here, we report safety and preliminary efficacy data from phase 2 of the ASTREON study, which evaluated 14-day Oral-AZA regimens in pts with Low ...

10. ashpublications.org ashpublications.org/blood/article/145/11/1126/534406/Efficacy-and-safety-of-venetoclax-plus-azacitidine

Efficacy and safety of venetoclax plus azacitidine for patients ... Venetoclax (14 days) + azacitidine regimen was well tolerated in patients with treatment-naive HR MDS, with no unexpected safety findings.