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

• ClinicalTrials.gov Identifier: NCT05362773
• Recruitment Status: Recruiting
• First Posted: May 5, 2022
• Last Update Posted: February 17, 2023
• Sponsor: MacroGenics
• Information provided by (Responsible Party): MacroGenics

Tracking Information

• First Submitted Date: May 2, 2022
• First Posted Date: May 5, 2022
• Last Update Posted Date: February 17, 2023
• Actual Study Start Date: July 13, 2022
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 2, 2022)

• Number of severe side effects in patients receiving MGD024 [ Time Frame: 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. [ Time Frame: Throughout study participation, up to 12 months. ]
  Observation of side effects determines the highest safe dose for further study

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 2, 2022)

• Maximum concentration [ Time Frame: 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) [ Time Frame: Day 1, 8,15, 22, 29, 36, 43, 50 and 57 ]
  Total body exposure to MGD024
• Anti-drug antibody formation [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Throughout study participation, up to 12 months. ]
• Number of participants with changes in cytokines or C-reactive protein after administration of tocilizumab. [ Time Frame: Throughout study participation, up to 12 months. ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of MGD024 in Patients With Relapsed or Refractory Hematologic Malignancies
• 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

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.

Study Arms

Experimental: Dose Escalation

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

Intervention: Drug: MGD024

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 2, 2022): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Global Trial Manager; 301-251-5172; info@macrogenics.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05362773
• Other Study ID Numbers: CP-MGD024-01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: MacroGenics
• Original Responsible Party: Same as current
• Current Study Sponsor: MacroGenics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ashley Ward, M.D.; MacroGenics

• PRS Account: MacroGenics
• Verification Date: August 2022