Clinical Trial - NCT03219268

       

A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms

Recruiting

Sponsor: MacroGenics

Collaborators: Zai Lab Co., Ltd.

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03219268

Protocol Info

Short Description: MGD013 IN UNRESECTABLE OR METASTATIC NEOPLASMS
Long Description: 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
MGH Status: Open
Sponsor: MacroGenics, Inc.
Disease Program: GI

Next Steps


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Purpose

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 Title Intervention Phase
Advanced Solid Tumors Hematologic Neoplasms Gastric Cancer Ovarian Cancer GastroEsophageal Cancer HER2-positive Breast Cancer HER2-positive Gastric Cancer DLBCL MGD013 MGD013 in combination with margetuximab Phase 1
Study Type Interventional
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

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (MGD013 monotherapy) [Time Frame: 24 months] [Designated as safety issue: ]

Maximum Tolerated Dose [Time Frame: 24 months] [Designated as safety issue: ]


Secondary Outcome Measures

Area Under the Plasma Concentration versus Time Curve (AUC) of MGD013 and MGD013 plus margetuximab [Time Frame: 24 months] [Designated as safety issue: ]

Maximum Plasma Concentration (Cmax) of MGD013 and MGD013 plus margetuximab [Time Frame: 24 months] [Designated as safety issue: ]

Time to reach maximum (peak) plasma concentration (Tmax) of MGD013 and MGD013 plus margetuximab [Time Frame: 24 months] [Designated as safety issue: ]

Trough plasma concentration (Ctrough) of MGD013 and MGD013 plus margetuximab [Time Frame: 24 months] [Designated as safety issue: ]

Total body clearance of the drug from plasma (CL) of MGD013 and MGD013 plus margetuximab [Time Frame: 24 months] [Designated as safety issue: ]

Apparent volume of distribution at steady state (Vss) of MGD013 and MGD013 plus margetuximab [Time Frame: 24 months] [Designated as safety issue: ]

Terminal half-life (t1/2) of MGD013 and MGD013 plus margetuximab [Time Frame: 24 months] [Designated as safety issue: ]

Percent of patients with anti-drug antibody [Time Frame: 24 months] [Designated as safety issue: ]

Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (MGD013 plus margetuximab) [Time Frame: 24 months] [Designated as safety issue: ]

Efficacy: Preliminary anti-tumor activity of MGD013 and MGD013 plus margetuximab [Time Frame: 36 months] [Designated as safety issue: ]

Overall survival [Time Frame: Up to 2 years after end of treatment visit] [Designated as safety issue: ]

Estimated Enrollment: 445
Study Start Date: August 2017
Estimated Study Completion Date: August 2022
Estimated Primary Completion Date: July 2021
Arms Assigned Interventions

Experimental:MGD013

MGD013 administered IV once every 2 or 3 weeks for up to 96 weeks
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 32 3-week cycles
Biological:MGD013 in combination with margetuximab
Anti-PD-1, anti-LAG-3 bispecific DART protein plus anti-HER2 monoclonal antibody

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03219268

Locations

  • United States, Arizona
    • Banner MD Anderson Cancer Center Gilbert, Arizona, United States, 85234
  • United States, California
    • USC/Norris Comprehensive Cancer Center Los Angeles, California, United States, 90033
    • UCLA Hematology & Oncology Clinic Los Angeles, California, United States, 90095
    • Hoag Memorial Hospital Presbyterian Newport Beach, California, United States, 92658
  • United States, Florida
    • Florida Cancer Specialists & Research Institute Sarasota, Florida, United States, 34232
  • United States, Illinois
    • University of Chicago Medicine Chicago, Illinois, United States, 60637
  • United States, Maryland
    • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland, United States, 21287
  • United States, Massachusetts
    • Massachusetts General Hospital and Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, North Carolina
    • Duke University Medical Center Durham, North Carolina, United States, 27710
  • United States, Ohio
    • Cincinnati Children's Hospital Medical Center Cincinnati, Ohio, United States, 45229
  • United States, Oklahoma
    • Stephenson Cancer Center, The University of Oklahoma Oklahoma City, Oklahoma, United States, 73104
  • United States, Pennsylvania
    • University of Pennsylvania, Abramson Cancer Center Philadelphia, Pennsylvania, United States, 19104
    • UPMC Hillman Cancer Center Pittsburgh, Pennsylvania, United States, 15232
  • United States, Tennessee
    • Sarah Cannon Research Institute Nashville, Tennessee, United States, 37203
  • United States, Texas
    • The University of Texas M.D. Anderson Cancer Center Houston, Texas, United States, 77030
  • Australia, New South Wales
    • St Vincent's Hospital Sydney Darlinghurst, New South Wales, Australia, 2010
    • Calvary Mater Newcastle Waratah, New South Wales, Australia, 2298
    • Southern Medical Day Care Centre Wollongong, New South Wales, Australia, 2500
  • Australia, Victoria
    • Austin Health Melbourne Heidelberg, Victoria, Australia, 3084
  • Bulgaria,
    • "Complex Oncology Center - Burgas" EOOD Burgas, , Bulgaria, 8000
    • "Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda" EAD, Sofia Sofia, , Bulgaria, 1407
    • Multiprofile Hospital for Active Treatment "Serdika" EOOD, Sofia Sofia, , Bulgaria, 1632
  • Poland,
    • BioVirtus Research Site Sp. Z o.o. Józefów, , Poland, 05-410
    • Pratia MCM Kraków Kraków, , Poland, 31-510
    • Med-Polonia Sp. z o.o. Poznan, , Poland, 60-693
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Warszawa, , Poland, 02-034
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Warszawa, , Poland, 02-781
  • Spain,
    • Vall d'Hebron Hospital Barcelona, , Spain, 08035
    • Hospital Ruber Internacional Madrid, , Spain, 28034
    • START Madrid-CIOCC, Hospital HM Sanchinarro Madrid, , Spain, 28050
  • Thailand,
    • King Chulalongkorn Memorial Hospital Bangkok, , Thailand, 10330
    • Maharaj Nakorn Chiang Mai Hospital Chiang Mai, , Thailand, 50200
    • Songklanagarind Hospital Songkhla, , Thailand, 90110
  • Ukraine,
    • Communal Nonprofit Enterprise Cherkasy Regional Oncology Dispensary Cherkasy, , Ukraine, 18009
    • Communal Non-profit Enterprise "City Clinical Hospital#4" of Dnipro City Council, Chemotherapy Department Dnipro, , Ukraine, 49102
    • Communal Nonprofit Enterprise "Prykarpatsky Clinical Oncological Centre of Ivano-Frankivska Regional Council" Ivano-Frankivs'k, , Ukraine, 76000
    • Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Dispensary" Sumy, , Ukraine, 40022
    • Communal Nonprofit Enterprise "Central City Clinical Hospital of Uzhhorod City Council" Uzhgorod, , Ukraine, 88000
    • Communal Nonprofit Enterprise Podillia Regional Center of Oncology of Vinniza Regional Council Vinnytsia, , Ukraine, 21029

Sponsors and Collaborators

MacroGenics

Zai Lab Co., Ltd.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03219268
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Additional relevant MeSH terms:

Neoplasms

Stomach Neoplasms

Hematologic Neoplasms

Neoplasm Metastasis

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on January 20, 2021