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Safety Study of MGD009 in B7-H3-expressing Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by MacroGenics
Sponsor:
Information provided by (Responsible Party):
MacroGenics
ClinicalTrials.gov Identifier:
NCT02628535
First received: November 20, 2015
Last updated: August 10, 2016
Last verified: August 2016
  Purpose
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 Intervention 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by MacroGenics:

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


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

  • 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

  • Change in tumor volume [ Time Frame: Weeks 6, 15, 24, 33, 42, 51, 60, 69, 78, 87, 96, 105 ]
    Anti-tumor activity of MGD006 using both conventional RECIST 1.1 and immune-related RECIST criteria.


Estimated Enrollment: 114
Study Start Date: September 2015
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MGD009
Humanized B7-H3 x CD3 Dual-Affinity Re-Targeting (DART®) Protein
Biological: MGD009
B7-H3 x CD3 DART protein

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.

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).

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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:
  • 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
  • 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 (e.g. require supplemental oxygen)
  • 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 Grave's disease that are now euthyroid clinically and by lab testing
  • History of clinically-significant cardiovascular disease
  • 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 4 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02628535

Contacts
Contact: Bing Nie 240-552-8084 nieb@macrogenics.com

Locations
United States, North Carolina
Carolina BioOncology Institute Recruiting
Huntersville, North Carolina, United States, 28078
Contact: Jaelyn Linski    704-947-6599 ext 111    jlinski@carolinabiooncology.org   
Principal Investigator: John D. Powderly, M.D.         
United States, Pennsylvania
Penn Presbyterian Medical Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Mona S Jacobs-Small, BS, RRT, CCRC    215-662-8632      
Principal Investigator: Evan Alley, M.D.         
United States, Texas
South Texas Accelerated Research Therapeutics, LLC Recruiting
San Antonio, Texas, United States, 78229
Contact: Leslie Smetzer    210-593-5269    leslie.smetzer@start.stoh.com   
Principal Investigator: Anthony Tolcher, M.D.         
Sponsors and Collaborators
MacroGenics
Investigators
Study Chair: James Vasselli, M.D. MacroGenics
  More Information

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT02628535     History of Changes
Other Study ID Numbers: CP-MGD009-01
Study First Received: November 20, 2015
Last Updated: August 10, 2016

Keywords provided by MacroGenics:
B7-H3-expressing neoplasms

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Pancreatic Neoplasms
Urinary Bladder Neoplasms
Carcinoma, Renal Cell
Mesothelioma
Thyroid Neoplasms
Sarcoma
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
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

ClinicalTrials.gov processed this record on April 28, 2017