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Safety Study of MGD009 in B7-H3-expressing Tumors

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. Identifier: NCT02628535
Recruitment Status : Recruiting
First Posted : December 11, 2015
Last Update Posted : March 6, 2019
Information provided by (Responsible Party):

Brief Summary:
The purpose of this study is to evaluate the safety of MGD009 when given to patients with B7-H3-expressing tumors. The study will also evaluate what is the highest dose of MGD009 that can be given safely. Assessments will be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics (PD) and to evaluate potential anti-tumor activity of MGD009.

Condition or disease Intervention/treatment Phase
Mesothelioma Bladder Cancer Melanoma Squamous Cell Carcinoma of the Head and Neck Non Small Cell Lung Cancer Clear Cell Renal Cell Carcinoma Ovarian Cancer Thyroid Cancer Breast Cancer Pancreatic Cancer Prostate Cancer Colon Cancer Soft Tissue Sarcoma Biological: MGD009 Phase 1

Detailed Description:

This study is a Phase 1 open-label, dose escalation, cohort expansion, and efficacy follow-up study of MGD009 administered intravenously (IV) on an every-other-week schedule for up to one year (14 cycles).

The dose escalation phase is designed to characterize the safety and tolerability of MGD009 and to define the maximum tolerated or maximum administered dose (MTD/MAD). This phase will enroll patients with mesothelioma, bladder cancer, melanoma, squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (ccRCC), ovarian cancer, thyroid cancer, triple-negative breast cancer (TNBC), pancreatic cancer, colon cancer, soft tissue sarcoma, or prostate cancer.

In the cohort expansion phase, 6 cohorts of 16 patients each will be enrolled to further evaluate the safety and potential efficacy of MGD009 administered at the MTD/MAD dose in patients with mesothelioma, bladder cancer, melanoma, SCCHN, NSCLC, or other specific tumors that express high levels of B7-H3. Pre- and on-study biopsies are required for melanoma patients in the cohort expansion phase. Two additional cohorts (up to15 patients each) will evaluate the use of prophylaxis therapies to mitigate toxicity.

The survival follow-up phase consists of the 2-year period after the final dose of study drug.

All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid Tumors (RECIST) and immune-related response criteria (irRC).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1, First-in-Human, Open Label, Dose Escalation Study of MGD009, A Humanized B7-H3 x CD3 Dual-Affinity Re-Targeting (DART) Protein in Patients With Unresectable or Metastatic B7-H3-Expressing Neoplasms
Study Start Date : September 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : March 2020

Arm Intervention/treatment
Experimental: MGD009
Orlotamab; Humanized B7-H3 x CD3 Dual-Affinity Re-Targeting (DART®) Protein
Biological: MGD009
B7-H3 x CD3 DART protein
Other Name: orlotamab

Primary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: 28 days after last dose of study drug ]
    adverse events, serious adverse events

Secondary Outcome Measures :
  1. Peak plasma concentration [ Time Frame: 8 days ]
    PK of MGD009

  2. Number of participants that develop anti-drug antibodies [ Time Frame: first dose through 28 days after last dose of study drug ]
    Proportion of patients who develop anti-MGD0009 antibodies, immunogenicity

  3. Change in tumor volume [ Time Frame: Weeks 6, 15, 24, 33, 42, 51, 60, 69, 78, 87, 96, 105 ]
    Anti-tumor activity of MGD009 using both conventional RECIST 1.1 and immune-related RECIST criteria.

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

Inclusion Criteria:

  • Histologically and/or cytologically proven unresectable locally advanced or metastatic tumors that express B7-H3 on the membrane or vasculature. The requirement for previous systemic therapy may be waived if a person was intolerant of standard front-line therapy
  • Dose escalation phase prior systemic treatment requirements:
  • pleural mesothelioma, pancreatic cancer: 1-3 prior treatments
  • urothelial, SCHNN, prostate, soft tissue sarcoma, prostate cancer, TNBC, ccRCC, NSCLC: 1-5 prior treatments
  • ovarian cancer: 2-4 prior treatments
  • colon cancer: 2-4 prior treatments
  • cutaneous melanoma: at least 1 prior treatment (including immunotherapy).
  • Patients with prior immune checkpoint inhibitors must have related toxicities reduced to Grade 0, 1, or baseline
  • Measurable disease per RECIST 1.1 criteria
  • Easter Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Acceptable laboratory parameters and adequate organ reserve.

Exclusion Criteria:

  • Patients with central nervous system (CNS) involvement must have been treated, be asymptomatic, do not exhibit progression of CNS metastases on MRI or CT within 28 days, and do not have concurrent leptomeningeal disease or cord compression.
  • Clinically significant pulmonary compromise within 28 days of first dose, including pneumonia, pneumonitis, requirement for supplemental oxygen). use to maintain adequate oxygenation, or pleural effusion sufficient to warrant pleurocentesis or any history of ≥ Grade 3 drug induced or radiation pneumonitis.
  • History of autoimmune disease with certain exceptions such as vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic therapy within the past 2 years, patients with history of Hashimoto's or Grave's disease that are now euthyroid clinically and by lab testing
  • History of clinically-significant cardiovascular disease, or cardiac arrhythmias, including atrial fibrillation at screening or day of treatment
  • History of clinically-significant gastrointestinal (GI) disease; GI perforation within 1 year; GI bleeding or acute pancreatitis within 3 months; or diverticulitis within 4 weeks of first study drug administration
  • Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days of first study drug administration
  • Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction (PCR)
  • Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome
  • History of allogeneic bone marrow, stem cell, or solid organ transplant
  • Treatment with systemic cancer therapy or investigational therapy within 3 weeks of first study drug administration; radiation within 2 weeks; corticosteroids (greater than or equal to 10 mg prednisone or equivalent per day) or other immune suppressive drugs within 2 weeks of first study drug administration
  • Trauma or major surgery within 4 weeks of first study drug administration
  • Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient contained in the drug or vehicle formulation for MGD009

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 identifier (NCT number): NCT02628535

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Contact: Amy Worth 240-660-0757

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United States, California
UCLA Active, not recruiting
Los Angeles, California, United States, 90095
Stanford University School of Medicine Recruiting
Palo Alto, California, United States, 94304
Contact: Feriel Buchholz    650-721-4090   
Principal Investigator: Shivaani Kummar, MD, FACP         
University of California - San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Luat Le    415-502-8075   
Principal Investigator: Lawrence Fong, MD         
United States, District of Columbia
Georgetown University Recruiting
Washington, District of Columbia, United States, 20007
Contact: Bridget Haley    202-687-6871   
Principal Investigator: Geoffrey Gibney, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Miriam McClung    617-726-1083   
Principal Investigator: Gregory Cote, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Steve Clark    617-582-7545      
Principal Investigator: F. Stephen Hodi, MD         
United States, New York
New York University Recruiting
New York, New York, United States, 10016
Contact: Peter Warren    646-754-7397      
Principal Investigator: Daniel Cho, MD         
Columbia University Medical Center Active, not recruiting
New York, New York, United States, 10032
United States, North Carolina
Carolina BioOncology Institute Active, not recruiting
Huntersville, North Carolina, United States, 28078
United States, Pennsylvania
Penn Presbyterian Medical Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Michael Galantino    215-662-8790   
Principal Investigator: Christine Ciunci, M.D.         
United States, Tennessee
Henry-Joyce Cancer Center Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact: Jordan Berlin, MD         
Principal Investigator: Jordan Berlin, MD         
United States, Texas
Mary Crowley Cancer Research Center Recruiting
Dallas, Texas, United States, 75230
Contact: Jessica Bondurant, BS    972-566-3065      
Principal Investigator: James Strauss, MD         
South Texas Accelerated Research Therapeutics, LLC Active, not recruiting
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22034
Contact: Kerly Lopez   
Principal Investigator: Alexander Spira, MD         
Australia, New South Wales
Chris O'Brien Lifehouse Active, not recruiting
Camperdown, New South Wales, Australia, 2050
Saint Vincent's Hospital Sydney Recruiting
Darlinghurst, New South Wales, Australia, 2010
Contact: Amy Prawira, MD   
Principal Investigator: Amy Prawira, MD         
Australia, Queensland
Princess Alexandra Hospital Active, not recruiting
Woolloongabba, Queensland, Australia, 4102
Australia, Victoria
Austin Health Active, not recruiting
Heidelberg, Victoria, Australia, 3084
Australia, Western Australia
Linear Clinical Research Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Tarek Meniawy, MD   
Principal Investigator: Tarek Meniawy, MD         
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G1Z5
Contact: Aaron Hansen, MD         
Principal Investigator: Aaron Hansen, MD         
Sponsors and Collaborators
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Study Chair: Stacie Goldberg, M.D. MacroGenics

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Responsible Party: MacroGenics Identifier: NCT02628535     History of Changes
Other Study ID Numbers: CP-MGD009-01
First Posted: December 11, 2015    Key Record Dates
Last Update Posted: March 6, 2019
Last Verified: March 2019

Keywords provided by MacroGenics:
B7-H3-expressing neoplasms

Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Pancreatic Neoplasms
Urinary Bladder Neoplasms
Carcinoma, Renal Cell
Thyroid Neoplasms
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Squamous Cell
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases