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A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03219268
Recruitment Status : Recruiting
First Posted : July 17, 2017
Last Update Posted : June 4, 2020
Sponsor:
Information provided by (Responsible Party):
MacroGenics

Tracking Information
First Submitted Date  ICMJE July 12, 2017
First Posted Date  ICMJE July 17, 2017
Last Update Posted Date June 4, 2020
Actual Study Start Date  ICMJE August 18, 2017
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2020)
  • Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (MGD013 monotherapy) [ 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.
  • Maximum Tolerated Dose [ Time Frame: 24 months ]
    maximum tolerated or maximum administered dose of MGD013
Original Primary Outcome Measures  ICMJE
 (submitted: July 14, 2017)
  • 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.
  • Maximum Tolerated Dose [ Time Frame: 24 months ]
    maximum tolerated or maximum administered dose of MGD013
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2020)
  • Area Under the Plasma Concentration versus Time Curve (AUC) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    AUC
  • Maximum Plasma Concentration (Cmax) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    Cmax
  • Time to reach maximum (peak) plasma concentration (Tmax) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    Tmax
  • Trough plasma concentration (Ctrough) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    Ctrough
  • Total body clearance of the drug from plasma (CL) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    CL
  • Apparent volume of distribution at steady state (Vss) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    Vss
  • Terminal half-life (t1/2) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]
    t1/2
  • Percent of patients with anti-drug antibody [ Time Frame: 24 months ]
    immunogenicity
  • Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (MGD013 plus margetuximab) [ Time Frame: 24 months ]
    Safety
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2017)
  • Area Under the Plasma Concentration versus Time Curve (AUC) of MGD013 [ Time Frame: 24 months ]
    AUC
  • Maximum Plasma Concentration (Cmax) of MGD013 [ Time Frame: 24 months ]
    Cmax
  • Time to reach maximum (peak) plasma concentration (Tmax) of MGD013 [ Time Frame: 24 months ]
    Tmax
  • Trough plasma concentration (Ctrough) of MGD013 [ Time Frame: 24 months ]
    Ctrough
  • Total body clearance of the drug from plasma (CL) of MGD013 [ Time Frame: 24 months ]
    CL
  • Apparent volume of distribution at steady state (Vss) of MGD013 [ Time Frame: 24 months ]
    Vss
  • Terminal half-life (t1/2) of MGD013 [ Time Frame: 24 months ]
    t1/2
  • Percent of patients with anti-drug antibody [ Time Frame: 24 months ]
    immunogenicity
  • Efficacy: Preliminary anti-tumor activity of MGD013 [ Time Frame: 36 months ]
    Preliminary anti-tumor activity of MGD013
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms
Official Title  ICMJE 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
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.
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 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. Two additional cohorts will enroll patients with gastric/gastroesophageal cancer or epithelial ovarian cancer, with MGD013 given every 3 weeks.

A separate cohort will evaluate the combination of MGD013 with margetuximab (anti-HER2 monoclonal antibody) in approximately 39 patients, in subgroups with HER2-positive gastric or gastroesophageal cancer, HER2-positive breast cancer, and any other HER2-positive cancer.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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
Condition  ICMJE
  • Advanced Solid Tumors
  • Hematologic Neoplasms
  • Gastric Cancer
  • Ovarian Cancer
  • GastroEsophageal Cancer
  • HER2-positive Breast Cancer
  • HER2-positive Gastric Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: MGD013
    MGD013 administered IV once every 2 or 3 weeks for up to 96 weeks
    Intervention: Biological: MGD013
  • Experimental: MGD013 plus margetuximab
    MGD013 administered in combination with margetuximab IV once every 3 weeks for up to 35 3-week cycles
    Interventions:
    • Biological: MGD013
    • Biological: MGD013 in combination with margetuximab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 12, 2020)
375
Original Estimated Enrollment  ICMJE
 (submitted: July 14, 2017)
131
Estimated Study Completion Date  ICMJE August 2022
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nadia Salem 202-834-0910 salemn@Macrogenics.com
Contact: Janine Koucheki (240) 224-4457 kouchekij@macrogenics.com
Listed Location Countries  ICMJE Australia,   Bulgaria,   Poland,   Spain,   Thailand,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03219268
Other Study ID Numbers  ICMJE CP-MGD013-01
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  ICMJE
Plan to Share IPD: Undecided
Responsible Party MacroGenics
Study Sponsor  ICMJE MacroGenics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Bradley Sumrow, MD MacroGenics
PRS Account MacroGenics
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP