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A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms

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ClinicalTrials.gov Identifier: NCT03219268
Recruitment Status : Recruiting
First Posted : July 17, 2017
Last Update Posted : July 17, 2019
Sponsor:
Information provided by (Responsible Party):
MacroGenics

Brief Summary:
The primary goal of this Phase 1 study is to characterize the safety and tolerability of MGD013 and establish the maximum tolerated dose (MTD) of MGD013. Pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and the anti-tumor activity of MGD013 will also be assessed.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Hematologic Neoplasms Biological: MGD013 Biological: MGD013 in combination with margetuximab Phase 1

Detailed Description:

This is a Phase 1, open-label, dose escalation and cohort expansion study designed to characterize the safety, tolerability, PK, PD, immunogenicity, and preliminary antitumor activity of MGD013 administered by IV infusion on every 2 weeks. The study consists of a Dose Escalation Phase to determine the MTD or maximum administered dose (MAD) of MGD013 if no MTD is defined, followed by a Cohort Expansion Phase to further define the safety and initial antitumor activity of MGD013 with the dose established in the Dose Escalation Phase.

In the Dose Escalation Phase, MGD013 will be evaluated in sequential escalating flat doses in successive cohorts of 1 to 6 patients each. Upon completion of the Dose Escalation Phase, a Cohort Expansion Phase will be initiated at the MTD/MAD.

Patients with unresectable, locally advanced or metastatic solid tumors of any histology will be enrolled in the Dose Escalation Phase. The Cohort Expansion Phase will be limited to selected cohorts of patients with unresectable, locally advanced or metastatic solid tumors or hematologic malignancies for whom there is no available therapy likely to confer clinical benefit.

A separate cohort will evaluate the combination of MGD013 with margetuximab (anti-HER2 monoclonal antibody) in approximately 12 patients with HER2-positive cancer.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 255 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Dose escalation followed by Cohort Expansion Phase at the MTD.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of MGD013, A Bispecific DART® Protein Binding PD-1 and LAG-3 in Patients With Unresectable or Metastatic Neoplasms
Actual Study Start Date : August 18, 2017
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : August 2022

Arm Intervention/treatment
Experimental: MGD013
MGD013 administered IV once every 2 weeks for up to 12 8-week cycles
Biological: MGD013
Anti-PD-1, anti-LAG-3 bispecific DART protein

Experimental: MGD013 plus margetuximab
MGD013 administered in combination with margetuximab IV once every 3 weeks for up to 35 3-week cycles
Biological: MGD013
Anti-PD-1, anti-LAG-3 bispecific DART protein

Biological: MGD013 in combination with margetuximab
Anti-PD-1, anti-LAG-3 bispecific DART protein plus anti-HER2 monoclonal antibody
Other Name: MGAH22




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 [ Time Frame: 24 months ]

    Safety

    Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.


  2. Maximum Tolerated Dose [ Time Frame: 24 months ]
    maximum tolerated or maximum administered dose of MGD013


Secondary Outcome Measures :
  1. Area Under the Plasma Concentration versus Time Curve (AUC) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    AUC

  2. Maximum Plasma Concentration (Cmax) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    Cmax

  3. Time to reach maximum (peak) plasma concentration (Tmax) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    Tmax

  4. Trough plasma concentration (Ctrough) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    Ctrough

  5. Total body clearance of the drug from plasma (CL) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    CL

  6. Apparent volume of distribution at steady state (Vss) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    Vss

  7. Terminal half-life (t1/2) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    t1/2

  8. Percent of patients with anti-drug antibody [ Time Frame: 24 months ]
    immunogenicity

  9. Efficacy: Preliminary anti-tumor activity of MGD013 and MGD013 plus margetuximab [ Time Frame: 36 months ]
    Preliminary anti-tumor activity of MGD013 and MGD013 plus margetuximab



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven, locally advanced unresectable or metastatic solid tumors (or hematologic malignancies, Cohort Expansion only) for whom no approved therapy with demonstrated clinical benefit is available or standard treatment was declined.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy ≥ 12 weeks
  • Measurable disease
  • Tissue specimen available for retrospective analysis of PD-1, PD-L1, LAG-3, and MHC-II expression
  • Acceptable laboratory parameters

HER2+ Cohort:

- Locally advanced or metastatic HER2+ locally advanced or metastatic solid tumors, regardless of organ of origin.

i. The cancer must have progressed following standard therapy, or has progressed during or after HER2-directed therapy if approved and available for patients with HER2+ breast or gastric cancer.

ii. History of HER2 positivity defined as 3+ by IHC or 2+ by IHC in combination with in situ hybridization (ISH) positivity most recent tumor biopsy.

Exclusion Criteria:

  • Symptomatic central nervous system (CNS) metastases or primary CNS lymphoma
  • History of allogeneic bone marrow, stem-cell, or solid organ transplant
  • History of known or suspected autoimmune disease with the specific exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment (within the past 2 years), and patients with a history of Grave's disease that are now euthyroid clinically and by laboratory testing.
  • Treatment with any systemic chemotherapy within 3 weeks prior to the initiation of study drug; treatment with biologics or investigational therapy within the 4 weeks prior to the initiation of study drug.
  • Major surgery within 4 weeks prior to the initiation of study drug.
  • Prior treatment with combination of monoclonal antibodies against PD-1 and LAG-3 (Cohort Expansion only).
  • Treatment with radiation therapy within 2 weeks prior to the initiation of study drug.
  • Clinically significant cardiovascular disease.
  • QTcF prolongation > 480 milliseconds
  • HER2+ cohort: left ventricular ejection fraction less than 50%
  • Clinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
  • Active pneumonitis or history of non-infectious pneumonitis.
  • Clinically significant gastrointestinal disorders.
  • Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug.
  • Known history of positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
  • Known history of hepatitis B (except in hepatocellular carcinoma) or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction (PCR)
  • Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed
  • Dementia or altered mental status that would preclude understanding and rendering of informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03219268


Contacts
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Contact: Janine Koucheki (240) 224-4457 kouchekij@macrogenics.com
Contact: Scott Currence (1) 240-552-8081 currences@macrogenics.com

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Sponsors and Collaborators
MacroGenics
Investigators
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Principal Investigator: Bradley Sumrow, MD MacroGenics

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Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT03219268     History of Changes
Other Study ID Numbers: CP-MGD013-01
First Posted: July 17, 2017    Key Record Dates
Last Update Posted: July 17, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hematologic Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms by Site
Hematologic Diseases
Neoplastic Processes
Pathologic Processes
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs