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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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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 / Treatment
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* Drug: MGD024


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Escalating doses of MGD024 will be assigned based on safety and tolerability of the previous dose level. | Drug: MGD024<br>* MGD024 is a CD123 x CD3 bispecific DART® molecule designed to target CD123-expressing leukemic cells for elimination by CD3-expressing T lymphocytes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration | The highest concentration of MGD024 at the end of the infusion | Day 1, 8,15, 22, 29, 36, 43, 50 and 57 | 
| Area under the concentration-time curve (AUC) | Total body exposure to MGD024 | Day 1, 8,15, 22, 29, 36, 43, 50 and 57 | 
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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. |