A Study of MGD024 in Patients With Relapsed or Refractory Hematologic Malignancies

Myelodysplastic Syndromes Clinical Trial

Official title:

A Phase 1, First-in-Human, Dose Escalation Study of MGD024, a CD123 x CD3 Bispecific DART Molecule, in Patients With Select Relapsed or Refractory Hematologic Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05362773
• Other study ID #: CP-MGD024-01
• Status: Recruiting
• Phase: Phase 1
• Start date: July 13, 2022
• Est. completion date: March 2025

Study information

• Verified date: January 2024
• Source: MacroGenics
• Contact: Global Trial Manager
• Phone: 301-251-5172
• Email: info[@]macrogenics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

CP-MGD024-01 is a Phase 1, open-label, multi-center study of MGD024 as a single agent in patients with select blood cancers that have not responded to treatment with standard therapies or who have relapsed after treatment. The study is designed to determine the safety, tolerability, pharmacokinetics (affect of the body on the drug), pharmacodynamic (affect of the drug on the body), immunogenicity (development of antibodies against the drug), and preliminary anti-cancer effect of MGD024.

Patients will receive treatment with MGD024 in consecutive 28-day cycles for a study treatment period of up to 12 cycles (approximately 1 year) or until treatment or study discontinuation criteria are met. Response assessments will be performed after Cycle 1 and then after every even numbered cycle starting with Cycle 2 until progression or study treatment discontinuation. Patients will be checked for side effects throughout the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients at least 18 years of age, able to provide informed consent and willing to comply with all study procedures.

• Patients with primary or secondary acute myeloid leukemia (AML), primary or secondary myelodysplastic syndrome (MDS), classical Hodgkin lymphoma (cHL), chronic myelogenous leukemia (CML), b-cell acute lymphocytic leukemia (B-ALL), hariy cell leukemia (HCL), advanced systemic mastocytosis (ASM), or blastic plasmacytoid dendritic cell neoplasm (BPDCM)

• Relapsed after or refractory to at least one prior line of therapy and with no available potentially curative treatment option.

• Evidence of CD123 expression

• Eastern Cooperative Oncology Group (ECOG) performance status of = 2.

• Life expectancy of at least 12 weeks.

• Acceptable laboratory values, and heart function.

• Continuing side effects of prior treatment are mild

• Women and men of childbearing potential must agree to use highly effective forms of contraception throughout the study through 4 months after the last dose of MGD024.

Exclusion Criteria:

• Prior treatment with an anti-CD123-directed agent (except patients with BPDCN, who are allowed to have received prior tagraxofusp).

• Known involvement of central nervous system (CNS) by the disease under investigation.

• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient.

• Systemic anti-cancer therapy, investigational therapy, corticosteroids or other immune suppressive drugs within 14 days of first dose

• Vaccination with any live virus vaccine within 4 weeks prior to first dose. Inactivated annual influenza and SARS-CoV-2 vaccination are allowed.

Related Conditions & MeSH terms

• Blastic Plasmacytoid Dendritic Cell Neoplasm
• Chronic Myeloid Leukemia
• Classical Hodgkin Lymphoma
• Hematologic Neoplasms
• Leukemia
• Leukemia, Acute Myeloid
• Leukemia, B-cell
• Leukemia, Hairy Cell
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid, Acute
• Mastocytosis
• Myelodysplastic Syndromes

Intervention

Drug:
• MGD024
MGD024 is a CD123 x CD3 bispecific DART® molecule designed to target CD123-expressing leukemic cells for elimination by CD3-expressing T lymphocytes.

Locations

Country	Name	City	State
United States	South Austin Medical Center	Austin	Texas
United States	University of Maryland, Greenbaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Colorado Blood Cancer Network	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	START - Midwest	Grand Rapids	Michigan
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of severe side effects in patients receiving MGD024	Observation of side effects determines the highest safe dose for further study	First 28 days of the study
Primary	Number and types of adverse events (AEs), including serious adverse events (SAEs), and AEs leading to treatment discontinuation.	Observation of side effects determines the highest safe dose for further study	Throughout study participation, up to 12 months.
Secondary	Maximum concentration	The highest concentration of MGD024 at the end of the infusion	Day 1, 8,15, 22, 29, 36, 43, 50 and 57
Secondary	Area under the concentration-time curve (AUC)	Total body exposure to MGD024	Day 1, 8,15, 22, 29, 36, 43, 50 and 57
Secondary	Anti-drug antibody formation	Number of patients who develop antibodies against MDG024	Day 1, Day 15, Day 28, then every 28 days throughout the study, up to 12 months.
Secondary	Overall response rate	The proportion of patients with a complete response or a partial response to treatment	Disease response assessment on Day 28, Day 56, then every 56 days throughout the study, up to 12 months.
Secondary	Complete response rate	The proportion of patient achieving a complete response according to disease-specific criteria	Disease response assessment on Day 28, Day 56, then every 56 days throughout the study, up to 12 months.
Secondary	Progression free survival	The time between the first dose date to the date of first documented disease-specific progression or death from any cause	Disease response is assessed approximately every 56 days throughout the study, up to 12 months.Assessed from Day 1 throughout the study until individual participant discontinuation, up to 12 months. Survival from Day 1 throughout the study.
Secondary	Time to response	The time between the first dose and the date of initial response.	Disease response is assessed approximately every 56 days throughout the study, up to 12 months.
Secondary	Duration of response	The time between the date of initial response to the date of disease-specific progression or death from any cause	Disease response is assessed approximately every 56 days throughout the study, up to 12 months.
Secondary	Overall survival	The time between the first dose date to the date of death from any cause	Assessed from Day 1 throughout the study until individual participant study discontinuation, up to 12 months.
Secondary	Number of participants with AEs and SAEs occurring after administration of tocilizumab		Throughout study participation, up to 12 months.
Secondary	Number of participants with changes in cytokines or C-reactive protein after administration of tocilizumab.		Throughout study participation, up to 12 months.