Evorpacept + Azacitidine for Myelodysplastic Syndrome

Recruiting at 18 trial locations

Overseen By Abraham Fong, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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

65 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase 1/2 clinical study will evaluate evorpacept (ALX148) in combination with azacitidine for the treatment of patients with higher risk myelodysplastic syndrome (MDS).

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.

What data supports the effectiveness of the drug combination Evorpacept and Azacitidine for treating Myelodysplastic Syndrome?

Azacitidine is a standard treatment for higher-risk myelodysplastic syndromes (MDS) and has shown effectiveness in improving response rates when combined with other drugs, such as lenalidomide, in similar conditions. Although specific data on Evorpacept is not provided, the combination approach with Azacitidine has been beneficial in related treatments. ^{1 2 3 4 5}

Is the combination of Evorpacept and Azacitidine safe for treating myelodysplastic syndrome?

Azacitidine, also known as Vidaza, has been shown to be generally safe in treating myelodysplastic syndromes, with common side effects including blood cell toxicity, stomach issues, and injection site reactions. However, there is no specific safety data available for the combination of Evorpacept and Azacitidine. ^{1 3 6 7 8}

What makes the drug combination of Evorpacept and Azacitidine unique for treating myelodysplastic syndrome?

The combination of Evorpacept and Azacitidine is unique because Evorpacept is a novel agent that blocks CD47/SIRPa, potentially enhancing the immune system's ability to target cancer cells, while Azacitidine is a standard treatment that blocks DNA synthesis in cancer cells. This combination may offer a new approach by targeting different mechanisms compared to existing treatments. ^{1 2 3 8 9}

Eligibility Criteria

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 am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. [2018]

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

The role of hypomethylating agents in myelodysplastic syndrome: changing the management paradigm. [2018]

3. England 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). [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Treatment of poor-risk myelodysplastic syndromes and acute myeloid leukemia with a combination of 5-azacytidine and valproic acid. [2021]

5. United States 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. [2022]

6. England 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. [2015]

7. New Zealand pubmed.ncbi.nlm.nih.gov

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

8. France pubmed.ncbi.nlm.nih.gov

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

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

Azacytidine for the treatment of myelodysplastic syndromes in the elderly. [2014]