Clinical trial NCT05362773: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: 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
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
First posted: 2022-05-05
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: CP-MGD024-01 is a Phase 1, open-label, multi-center study of MGD024 as a single agent in participants 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.

Participants 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. Participants will be checked for side effects throughout the study.


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.
* Participants with

  * primary or secondary acute myeloid leukemia (AML) except acute promyelocytic leukemia,
  * primary or secondary myelodysplastic syndrome (MDS) with prognostic score of \>3 and \<20% bone marrow blasts,
  * 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 at least 20% of malignant cells with 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.

Primary outcomes:
measure: Number of severe side effects in patients receiving MGD024
timeFrame: First 28 days of the study
measure: Number and types of adverse events (AEs), including serious adverse events (SAEs), and AEs leading to treatment discontinuation.
timeFrame: Throughout study participation, up to 12 months.
Secondary outcomes:
measure: Mean maximum concentration
timeFrame: Throughout study participation, up to 12 months.
measure: Mean area under the concentration-time curve (AUC)
timeFrame: Throughout study participation, up to 12 months.
measure: Number of participants with anti-drug antibody formation
timeFrame: Throughout study participation, up to 12 months.
measure: Overall response rate
timeFrame: Disease response assessment on Day 28, Day 56, then every 56 days throughout the study, up to 12 months.
measure: Complete response rate
timeFrame: Disease response assessment on Day 28, Day 56, then every 56 days throughout the study, up to 12 months.
measure: Median progression free survival
timeFrame: 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.
measure: Median time to response
timeFrame: Disease response is assessed approximately every 56 days throughout the study, up to 12 months.
measure: Median duration of response
timeFrame: Disease response is assessed approximately every 56 days throughout the study, up to 12 months.
measure: Overall survival
timeFrame: Assessed from Day 1 throughout the study until individual participant study discontinuation, up to 12 months.
measure: Number of participants with AEs and SAEs occurring after administration of tocilizumab or etanercept for cytokine release syndrome (CRS)
timeFrame: Throughout study participation, up to 12 months.
measure: Number of participants with changes in cytokines or C-reactive protein after administration of tocilizumab or etanercept
timeFrame: Throughout study participation, up to 12 months.
measure: Outcome of CRS event in participants treated with tocilizumab or etanercept
timeFrame: Throughout study participation, up to 12 months.
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Network
state: Colorado
city: Baltimore
country: United States
facility: University of Maryland, Greenbaum Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Grand Rapids
country: United States
facility: START - Midwest
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Austin
country: United States
facility: South Austin Medical Center
state: Texas
Study officials:
affiliation: MacroGenics
name: Ashley Ward, M.D.
role: STUDY_DIRECTOR
References: