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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03219268
Recruitment Status : Active, not recruiting
First Posted : July 17, 2017
Last Update Posted : June 21, 2022
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 21, 2022
Actual Study Start Date  ICMJE August 18, 2017
Estimated Primary Completion Date February 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 11, 2022)
  • Incidence of Treatment-Emergent Adverse Events (TEAE) as assessed by CTCAE v4.03 (tebotelimab monotherapy) [ Time Frame: up to 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: up to 24 months ]
    maximum tolerated or maximum administered dose of tebotelimab
  • Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (tebotelimab plus margetuximab) [ Time Frame: up to 24 months ]
    Safety
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: April 11, 2022)
  • Area Under the Plasma Concentration versus Time Curve (AUC) of tebotelimab [ Time Frame: From Day 1 to Day 15 after the first and second doses ]
    AUC
  • Maximum Plasma Concentration (Cmax) of tebotelimab and tebotelimab plus margetuximab [ Time Frame: At the end of infusion on Study Days 1, 15, 29 and 43 in Cycles 1 and 2 and on Study Day 1 for all subsequent cycles until treatment discontinuation, up to 2 years ]
    Cmax
  • Time to reach maximum (peak) plasma concentration (Tmax) of tebotelimab and tebotelimab plus margetuximab [ Time Frame: At the end of infusion on Study Days 1, 15, 29 and 43 in Cycles 1 and 2 and on Study Day 1 for all subsequent cycles until treatment discontinuation, up to 2 years ]
    Tmax
  • Trough plasma concentration (Ctrough) of tebotelimab [ Time Frame: Study Days 1, 15, 29, 43 in Cycles 1 and 2 and Day 1 of each subsequent cycle s until treatment discontinuation, up to 2 years ]
    Ctrough
  • Total body clearance of the drug from plasma (CL) of tebotelimab [ Time Frame: Cycle 1 Day 1 out to Cycle 1 Day 15 ]
    CL
  • Apparent volume of distribution at steady state (Vss) of tebotelimab [ Time Frame: Cycle 1 Day 1 out to Cycle 1 Day 15 ]
    Vss
  • Terminal half-life (t1/2) of tebotelimab [ Time Frame: Cycle 1 Day 1 out to Cycle 1 Day 15 ]
    t1/2
  • Percent of patients with anti-drug antibody [ Time Frame: Study Day 1, 15, 29, 57, 85, 113, then every 56 days up to 2 years Tebotelimab plus margetuximab: Day 1, 22, 43, and then every 6 weeks until treatment discontinuation ]
    immunogenicity
  • Objective response rate (ORR) [ Time Frame: Assessed every 6 weeks for the first 6 months, then every 12 weeks for up to 2 years. ]
    ORR is the percentage of participants who have a complete response or a partial response to treatment.
  • Duration of response (DoR) [ Time Frame: Assessed every 6 weeks for the first 6 months, then every 12 weeks for up to 2 years. ]
    DoR is defined as the time from the date of initial response (CR or PR) to the date of first documented PD or death from any cause, whichever occurs first.
  • Progression-free survival (PFS) [ Time Frame: Assessed every 6 weeks for the first 6 months, then every 12 weeks for up to 2 years. ]
    PFS is defined as the time from the first dose date to the date of first documented PD or death from any cause, whichever occurs first.
  • Overall survival (OS) [ Time Frame: Survival status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 2 years ]
    OS is defined as the time from the first dose date to the date of death from any cause
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 tebotelimab and establish the maximum tolerated dose (MTD) of tebotelimab in advanced solid tumors, and tebotelimab in combination with margetuximab in HER2+ advanced solid tumors. Pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and the anti-tumor activity of tebotelimab will also be assessed.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumors
  • Hematologic Neoplasms
  • Ovarian Cancer
  • HER2-positive Advanced Solid Tumors
  • Non Small Cell Lung Cancer
  • Small-cell Lung Cancer
  • Squamous Cell Carcinoma of Head and Neck
  • Cholangiocarcinoma
  • Cervical Cancer
  • TNBC - Triple-Negative Breast Cancer
Intervention  ICMJE
  • Biological: tebotelimab
    Anti-PD-1, anti-LAG-3 bispecific DART protein
    Other Name: MGD013
  • Biological: margetuximab
    anti-HER2 monoclonal antibody
    Other Names:
    • MGAH22
    • Margenza®
Study Arms  ICMJE
  • Experimental: Dose level 1
    Tebotelimab administered IV once every 2 weeks for up to 96 weeks
    Intervention: Biological: tebotelimab
  • Experimental: Dose level 2
    Tebotelimab administered IV once every 2 weeks for up to 96 weeks
    Intervention: Biological: tebotelimab
  • Experimental: Dose level 3
    Tebotelimab administered IV once every 2 weeks for up to 96 weeks
    Intervention: Biological: tebotelimab
  • Experimental: Dose level 4
    Tebotelimab administered IV once every 2 weeks for up to 96 weeks
    Intervention: Biological: tebotelimab
  • Experimental: Dose level 5
    Tebotelimab administered IV once every 2 weeks for up to 96 weeks
    Intervention: Biological: tebotelimab
  • Experimental: Dose level 6
    Tebotelimab administered IV once every 2 weeks for up to 96 weeks
    Intervention: Biological: tebotelimab
  • Experimental: Dose level 7
    Tebotelimab administered IV once every 2 weeks for up to 96 weeks
    Intervention: Biological: tebotelimab
  • Experimental: Dose level 8
    Tebotelimab administered IV once every 2 weeks for up to 96 weeks
    Intervention: Biological: tebotelimab
  • Experimental: Dose level 9
    Tebotelimab administered in combination with margetuximab IV once every 3 weeks for up to 32 3-week cycles
    Interventions:
    • Biological: tebotelimab
    • Biological: margetuximab
  • Experimental: Dose level 10
    Tebotelimab administered in combination with margetuximab IV once every 3 weeks for up to 32 3-week cycles
    Interventions:
    • Biological: tebotelimab
    • Biological: 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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 28, 2021)
353
Original Estimated Enrollment  ICMJE
 (submitted: July 14, 2017)
131
Estimated Study Completion Date  ICMJE February 2023
Estimated Primary Completion Date February 2023   (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, gastric, or gastroesophageal junction cancer.

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

  • All patients in the HER2+ cohort must be willing to provide consent for a baseline and on-treatment tumor biopsy during the screening period and within 14 days prior to Cycle 3 Day 1. Exceptions may be made based on a medical contraindication at the discretion of the Sponsor's Medical Monitor. This requirement will be discontinued after an adequate number of samples are collected, as determined by the Sponsor.

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
  • Confirmed or presumed COVID-19/SARS-CoV-2 infection. While SARS-CoV-2 testing is not mandatory for study entry, testing should follow local clinical practice guidelines/standards. Patients with a positive test result for SARS-CoV-2 infection, known asymptomatic infection, or presumed infection are excluded. Patients may be considered eligible after a resolved SARS-CoV-2 infection once he or she remains afebrile for at least 72 hours and after other SARS-CoV-2-related symptoms have fully recovered to baseline for a minimum of 72 hours.
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Bulgaria,   Hong Kong,   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: No
Current Responsible Party MacroGenics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE MacroGenics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ashley Ward, MD MacroGenics
PRS Account MacroGenics
Verification Date June 2022

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