A Study of Oral Decitabine/Cedazuridine in Combination With Magrolimab in Participants With Intermediate- to Very High-Risk Myelodysplastic Syndromes (MDS)

Astex Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Myelodysplastic Syndromes

Treatments: Drug: Decitabine/Cedazuridine; Drug: Magrolimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05835011

2022-501548-14-00 (Other Identifier)

ASTX727-10

Details and patient eligibility

About

The primary purpose of the study is to evaluate the preliminary safety and efficacy of oral decitabine/cedazuridine in combination with magrolimab.

Enrollment: 2 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Histological confirmation of previously untreated MDS (i.e., no hypomethylating agent [HMA], chemotherapy, or allogenic stem cell transplant [SCT] per World Health Organization 2016 classification with <20% bone marrow (BM) blasts per marrow biopsy/aspirate at screening.
2. Projected life expectancy of at least 3 months.
3. Overall Revised International Prognostic Scoring System for myelodysplastic syndromes (IPSS-R) score ≥3.5 MDS (immediate risk or higher).
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.
5. Hematopoietic stem cell transplant (HSCT) eligible without any pre-arranged HSCT on Cycle 1 Day 1, or HSCT ineligible.
6. Blood type and screen (any of the 4 blood groups A, B, AB, and O [ABO]/rhesus factor [Rh]) along with extended red blood cell phenotyping or genotyping completed prior to study drug treatment.
7. Hemoglobin ≥9 grams per deciliter (g/dL) on the first day of drug administration, transfusions allowed.
8. Willing to undergo blood transfusions as per parameters of protocol and clinically necessary.
9. White blood cell count ≤20×103/microliters (μL) prior to first dose and throughout study. Hydroxyurea could have been used to achieve this goal prior to and during the first 56 days of magrolimab administration.

Exclusion criteria

• Medical Conditions:

1. Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive), or hepatitis C (e.g., hepatitis C virus ribonucleic acid [HCV RNA] is detected), or chronic hepatitis B or C infection or human immunodeficiency virus (HIV) infection in medical history, with the following exceptions:

   1. Those with a history of hepatitis with a negative polymerase chain reaction (either qualitative or quantitative) OR have documentation of stable disease with aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase <2.0×upper limit of normal (ULN) may be eligible for this study.
   2. Participants with history of HIV who have an undetectable viral load for the prior 3 months, and who agree to maintain antiviral therapy, may be eligible for the study.

2. Significant medical diseases or conditions, as assessed by the investigators and sponsor, that would substantially increase the risk benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV.

3. Known inherited or acquired bleeding disorders that require medication or medical intervention.

4. Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which participants are not on active anticancer therapies and have had no evidence of active malignancy for at least ≥1 year.

   -Prior/Concomitant Therapy:

5. Immediate eligibility for an allogeneic SCT, as determined by the investigator, with an available donor.

6. Prior therapy for MDS with chemotherapy, allogenic SCT, or ≥1 full cycle of treatment with any HMA.

7. History of therapy-related MDS, MDS evolving from a pre-existing myeloproliferative neoplasm (MPN), MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia, juvenile myelomonocytic leukemia, and unclassifiable MDS/MPN.

8. Prior anti-cluster of differentiation 47 (CD47) treatment.

9. Previous SCT within 6 months before first dose administration, active graft-versus-host disease, or requiring transplant-related immunosuppression.

   -Other Exclusions:

10. Known or suspected hypersensitivity to decitabine, cedazuridine, magrolimab, or any of their excipients.

11. Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the participant to high-risk of noncompliance with the protocol.

12. Clinical suspicion of active central nervous system (CNS) involvement by MDS.

13. History of psychiatric illness or substance abuse likely to interfere with the ability to comply with protocol requirements or give informed consent.

14. Pregnant or actively breastfeeding.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

Oral Decitabine/Cedazuridine + Magrolimab

Experimental group

Description:

Participants will receive 35 milligrams (mg) decitabine/100 mg cedazuridine as a fixed dose combination (FDC) tablet, orally, once daily (QD) on Days 1-5 of each 28-day cycle in combination with magrolimab, intravenous (IV) infusion of 1 milligrams per kilogram (mg/kg) on Days 1 and 4, 15 mg/kg on Day 8, 30 mg/kg on Days 11, 15, 22, 29, 36, 43, and 50, followed by a maintenance dose of 30 mg/kg on Day 57 and every 14 days thereafter until toxicity, progressive disease, withdrawal, death or end of study (approximately 44 months).

Treatment:

Drug: Magrolimab

Drug: Decitabine/Cedazuridine