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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02628535
Recruitment Status : Active, not recruiting
First Posted : December 11, 2015
Last Update Posted : August 13, 2019
Sponsor:
Information provided by (Responsible Party):
MacroGenics

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.



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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 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 ClinicalTrials.gov identifier (NCT number): NCT02628535


Locations
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United States, California
UCLA
Los Angeles, California, United States, 90095
Stanford University School of Medicine
Palo Alto, California, United States, 94304
University of California - San Francisco
San Francisco, California, United States, 94143
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20007
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
New York University
New York, New York, United States, 10016
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Carolina BioOncology Institute
Huntersville, North Carolina, United States, 28078
United States, Pennsylvania
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Henry-Joyce Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
Mary Crowley Cancer Research Center
Dallas, Texas, United States, 75230
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Cancer Specialists
Fairfax, Virginia, United States, 22034
Australia, New South Wales
Chris O'Brien Lifehouse
Camperdown, New South Wales, Australia, 2050
Saint Vincent's Hospital Sydney
Darlinghurst, New South Wales, Australia, 2010
Australia, Queensland
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, Victoria
Austin Health
Heidelberg, Victoria, Australia, 3084
Australia, Western Australia
Linear Clinical Research
Nedlands, Western Australia, Australia, 6009
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G1Z5
Sponsors and Collaborators
MacroGenics
Investigators
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Study Chair: Stacie Goldberg, M.D. MacroGenics

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Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT02628535     History of Changes
Other Study ID Numbers: CP-MGD009-01
First Posted: December 11, 2015    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019
Keywords provided by MacroGenics:
B7-H3-expressing neoplasms
Additional relevant MeSH terms:
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Carcinoma
Sarcoma
Carcinoma, Renal Cell
Mesothelioma
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Carcinoma, Squamous Cell
Neoplasms, Connective and Soft Tissue
Urologic Neoplasms
Urologic Diseases
Adenocarcinoma
Kidney Neoplasms
Kidney Diseases
Head and Neck Neoplasms
Adenoma
Neoplasms, Mesothelial