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

Sponsor

MacroGenics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05362773

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

22.5

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Acute Myeloid Myelodysplastic Syndromes Classical Hodgkin Lymphoma Leukemia, B-cell Leukemia, Hairy Cell Mastocytosis, Aggressive Systemic Blastic Plasmacytoid Dendritic Cell Neoplasm Chronic Myeloid Leukemia	Drug: MGD024	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation Escalating doses of MGD024 will be assigned based on safety and tolerability of the previous dose level.	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.

Arm

Intervention/Treatment

Experimental: Dose Escalation

Escalating doses of MGD024 will be assigned based on safety and tolerability of the previous dose level.

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.

Outcome Measures

Primary Outcome Measures

Number of severe side effects in patients receiving MGD024 [First 28 days of the study]
Observation of side effects determines the highest safe dose for further study
Number and types of adverse events (AEs), including serious adverse events (SAEs), and AEs leading to treatment discontinuation. [Throughout study participation, up to 12 months.]
Observation of side effects determines the highest safe dose for further study

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Colorado Blood Cancer Network	Denver	Colorado	United States	80218
2	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
3	South Texas Accelerated Research Therapeutics, LLC - Midwest	Grand Rapids	Michigan	United States	49503
4	Duke University Medical Center	Durham	North Carolina	United States	27710