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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

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.

Condition or disease Intervention/treatment Phase
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 Biological: tebotelimab Biological: margetuximab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 353 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
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 : February 2023
Estimated Study Completion Date : February 2023


Arm Intervention/treatment
Experimental: Dose level 1
Tebotelimab administered IV once every 2 weeks for up to 96 weeks
Biological: tebotelimab
Anti-PD-1, anti-LAG-3 bispecific DART protein
Other Name: MGD013

Experimental: Dose level 2
Tebotelimab administered IV once every 2 weeks for up to 96 weeks
Biological: tebotelimab
Anti-PD-1, anti-LAG-3 bispecific DART protein
Other Name: MGD013

Experimental: Dose level 3
Tebotelimab administered IV once every 2 weeks for up to 96 weeks
Biological: tebotelimab
Anti-PD-1, anti-LAG-3 bispecific DART protein
Other Name: MGD013

Experimental: Dose level 4
Tebotelimab administered IV once every 2 weeks for up to 96 weeks
Biological: tebotelimab
Anti-PD-1, anti-LAG-3 bispecific DART protein
Other Name: MGD013

Experimental: Dose level 5
Tebotelimab administered IV once every 2 weeks for up to 96 weeks
Biological: tebotelimab
Anti-PD-1, anti-LAG-3 bispecific DART protein
Other Name: MGD013

Experimental: Dose level 6
Tebotelimab administered IV once every 2 weeks for up to 96 weeks
Biological: tebotelimab
Anti-PD-1, anti-LAG-3 bispecific DART protein
Other Name: MGD013

Experimental: Dose level 7
Tebotelimab administered IV once every 2 weeks for up to 96 weeks
Biological: tebotelimab
Anti-PD-1, anti-LAG-3 bispecific DART protein
Other Name: MGD013

Experimental: Dose level 8
Tebotelimab administered IV once every 2 weeks for up to 96 weeks
Biological: tebotelimab
Anti-PD-1, anti-LAG-3 bispecific DART protein
Other Name: MGD013

Experimental: Dose level 9
Tebotelimab administered in combination with margetuximab IV once every 3 weeks for up to 32 3-week cycles
Biological: tebotelimab
Anti-PD-1, anti-LAG-3 bispecific DART protein
Other Name: MGD013

Biological: margetuximab
anti-HER2 monoclonal antibody
Other Names:
  • MGAH22
  • Margenza®

Experimental: Dose level 10
Tebotelimab administered in combination with margetuximab IV once every 3 weeks for up to 32 3-week cycles
Biological: tebotelimab
Anti-PD-1, anti-LAG-3 bispecific DART protein
Other Name: MGD013

Biological: margetuximab
anti-HER2 monoclonal antibody
Other Names:
  • MGAH22
  • Margenza®




Primary Outcome Measures :
  1. 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.


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

  3. Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (tebotelimab plus margetuximab) [ Time Frame: up to 24 months ]
    Safety


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. Total body clearance of the drug from plasma (CL) of tebotelimab [ Time Frame: Cycle 1 Day 1 out to Cycle 1 Day 15 ]
    CL

  6. Apparent volume of distribution at steady state (Vss) of tebotelimab [ Time Frame: Cycle 1 Day 1 out to Cycle 1 Day 15 ]
    Vss

  7. Terminal half-life (t1/2) of tebotelimab [ Time Frame: Cycle 1 Day 1 out to Cycle 1 Day 15 ]
    t1/2

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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, 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.

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


Locations
Show Show 40 study locations
Sponsors and Collaborators
MacroGenics
Investigators
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Study Director: Ashley Ward, MD MacroGenics
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Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT03219268    
Other Study ID Numbers: CP-MGD013-01
First Posted: July 17, 2017    Key Record Dates
Last Update Posted: June 21, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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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Neoplasms
Lung Neoplasms
Small Cell Lung Carcinoma
Triple Negative Breast Neoplasms
Cholangiocarcinoma
Squamous Cell Carcinoma of Head and Neck
Hematologic Neoplasms
Neoplasm Metastasis
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Breast Neoplasms
Breast Diseases
Skin Diseases
Adenocarcinoma
Head and Neck Neoplasms
Hematologic Diseases
Neoplastic Processes
Pathologic Processes
Margetuximab
Antineoplastic Agents