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

NCT05835011 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: ASTX727-102022-501548-14-00
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Adverse Events (AEs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0

  An AE is any untoward medical occurrence in a subject or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention.

  From signing of informed consent to 30 days after last dose of study drug (Up to 8 weeks)

• Number of Participants With Dose-Limiting Toxicities (DLTs)

  DLTs are defined as any of the following toxicities at least possibly related to the treatment regimen: drug-related Grade ≥3 non-hematologic event; grade 4 neutropenia and thrombocytopenia that was not present prior to dosing, that last 28 days or longer and is not related to underlying disease; or any drug-related toxicity that result in treatment delay of \>2 weeks after Cycle 1 (28 days) is complete.

  From signing of informed consent to 30 days after last dose of study drug (Up to 8 weeks)

• Complete Response (CR) Rate

  CR defined as per International Working Group (IWG) criteria 2006: Bone marrow (BM) ≤5% myeloblasts with normal maturation of all cell lines; Persistent dysplasia; Peripheral blood; Hemoglobin (Hgb) ≥11 g/dL; Platelets ≥100×109/L; Neutrophils ≥1.0×109/Lb; Blasts 0%. Per the response criteria the response must last ≥4 weeks.

  Up to 44 months

Secondary Outcomes (10)

• Area Under the Plasma Concentration-Time Curve (AUC) of Oral Decitabine/Cedazuridine and Magrolimab

  Decitabine/Cedazuridine: Multiple timepoints pre-dose and post dose up to Day 5 of Cycle 1 and Day 4 of Cycle 2 (Cycle=28 days); Magrolimab: Multiple timepoints pre-dose and post dose up to end of treatment (up to 44 months)

• Overall Response Rate (ORR)

  Up to 44 months

• Rate of Hematologic Improvement (HI)

  Up to 44 months

• Duration of Progression Free Survival (PFS)

  Up to 44 months

• Leukemia-free Survival (LFS)

  Up to 44 months

Study Arms (1)

Oral Decitabine/Cedazuridine + Magrolimab

EXPERIMENTAL

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).

Drug: Decitabine/Cedazuridine; Drug: Magrolimab

Interventions

Decitabine/Cedazuridine DRUG

Oral FDC tablets administration

Also known as: ASTX727, INQOVI

Oral Decitabine/Cedazuridine + Magrolimab

Magrolimab DRUG

IV administration

Also known as: Hu5F9-G4

Oral Decitabine/Cedazuridine + Magrolimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Projected life expectancy of at least 3 months.
• Overall Revised International Prognostic Scoring System for myelodysplastic syndromes (IPSS-R) score ≥3.5 MDS (immediate risk or higher).
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.
• Hematopoietic stem cell transplant (HSCT) eligible without any pre-arranged HSCT on Cycle 1 Day 1, or HSCT ineligible.
• 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.
• Hemoglobin ≥9 grams per deciliter (g/dL) on the first day of drug administration, transfusions allowed.
• Willing to undergo blood transfusions as per parameters of protocol and clinically necessary.
• 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.

You may not qualify if:

• \- Medical Conditions:
• 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:
• 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.
• 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.
• 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.
• Known inherited or acquired bleeding disorders that require medication or medical intervention.
• 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:
• Immediate eligibility for an allogeneic SCT, as determined by the investigator, with an available donor.
• Prior therapy for MDS with chemotherapy, allogenic SCT, or ≥1 full cycle of treatment with any HMA.
• 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.
• Prior anti-cluster of differentiation 47 (CD47) treatment.
• Previous SCT within 6 months before first dose administration, active graft-versus-host disease, or requiring transplant-related immunosuppression.
• Known or suspected hypersensitivity to decitabine, cedazuridine, magrolimab, or any of their excipients.
• 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.

Sponsors & Collaborators

• Astex Pharmaceuticals, Inc.: lead

Study Sites (3)

Yale University

New Haven, Connecticut, 06520, United States

Location

BRCR Medical Center

Plantation, Florida, 33322, United States

Location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

decitabine and cedazuridine drug combination; magrolimab

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

The study was terminated prematurely due to discontinuation of magrolimab development in MDS.

Results Point of Contact

• Title: Taiho Central
• Organization: Taiho Oncology, Inc.

medicalinformation@taihooncology.com

844-878-2446

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2023
• First Posted: April 28, 2023
• Study Start: June 27, 2023
• Primary Completion: August 21, 2023
• Study Completion: August 21, 2023
• Last Updated: October 2, 2024
• Results First Posted: October 2, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)