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Safety Study of Enoblituzumab (MGA271) in Combination With Ipilimumab in Refractory Cancer

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ClinicalTrials.gov Identifier: NCT02381314
Recruitment Status : Active, not recruiting
First Posted : March 6, 2015
Last Update Posted : March 6, 2018
Sponsor:
Information provided by (Responsible Party):
MacroGenics

Brief Summary:
The purpose of this study is to evaluate the safety of enoblituzumab (MGA271) in combination with Yervoy (ipilimumab) when given to patients with B7-H3-expressing melanoma, squamous cell carcinoma of the head and neck (SCCHN), non small cell lung cancer (NSCLC) and other B7-H3 expressing cancers. The study will also evaluate what is the best dose of enoblituzumab to use when given with ipilimumab. Assessments will also be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics) and to evaluate potential anti-tumor activity of enoblituzumab in combination with ipilimumab.

Condition or disease Intervention/treatment Phase
Melanoma Non Small Cell Lung Cancer Biological: enoblituzumab plus ipilimumab Phase 1

Detailed Description:

This study is a Phase 1 open-label, dose escalation, and cohort expansion study of enoblituzumab administered intravenously (IV) on a weekly schedule for up to 51 doses in combination with IV ipilimumab administered on an every-3-week schedule for 4 doses.

The dose escalation phase is designed to characterize the safety and tolerability of the combination of enoblituzumab and ipilimumab and to define the maximum tolerated or administered dose (MTD/MAD) in patients with B7-H3 expressing mesothelioma, urothelial cancer, NSCLC, SCCHN, Clear cell renal cell carcinoma (ccRCC), ovarian cancer, melanoma, thyroid cancer, Triple negative breast cancer (TNBC), pancreatic cancer, colon cancer, soft tissue sarcoma, or prostate cancer.

The cohort expansion phase, 2 cohorts of 16 patients each will be enrolled to further evaluate the safety and potential efficacy of the combination administered at the MTD/MAD dose in patients with melanoma and NSCLC.

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


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 59 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Dose Escalation Study of MGA271 in Combination With Ipilimumab in Patients With Melanoma, Non-Small Cell Lung Cancer, and Other Cancers
Actual Study Start Date : March 26, 2015
Actual Primary Completion Date : November 9, 2017
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
Drug Information available for: Ipilimumab
U.S. FDA Resources

Arm Intervention/treatment
Experimental: enoblituzumab plus ipilimumab
Enoblituzumab: Fc-optimized, humanized monoclonal antibody. Ipilimumab: Yervoy; recombinant, fully humanized IgG-1 CTLA-4 blocking antibody approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of unresectable or metastatic melanoma.
Biological: enoblituzumab plus ipilimumab
enoblituzumab is administered by IV infusion once per week. Ipilimumab is administered by IV infusion every 3 weeks for up to 4 doses.
Other Name: enoblituzumab (MGA271); ipilimumab (Yervoy)



Primary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: 1 year ]
    Adverse events, serious adverse events


Secondary Outcome Measures :
  1. Peak plasma concentration [ Time Frame: 7 weeks ]
    PK of MGA271 in combination with ipilimumab

  2. Number of participants that develop anti-drug antibodies [ Time Frame: 7 weeks ]
    Proportion of patients who develop anti-MGA271 antibodies, immunogenicity

  3. Change in tumor volume [ Time Frame: Weeks 9, 18, 27, 39, and 51 ]
    Anti-tumor activity of MGA271 in combination with ipilimumab using both conventional RECIST 1.1 and immune-related RECIST criteria.



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria - Cohort Expansion Phase:

  • Histologically-proven, unresectable, locally advanced or metastatic melanoma or NSCLC

    • Melanoma: Advanced or metastatic melanoma patients may be systemic therapy naïve or may have received systemic treatment for unresectable locally advanced or metastatic disease. A patient who previously received systemic therapy must have had progression on a checkpoint inhibitor (e.g., anti-PD-L1, anti-PD-1, anti-CTLA-4) as the most recent prior therapy.
    • NSCLC: NSCLC that has progressed during or following 1 or more prior systemic therapies for unresectable locally advanced or metastatic disease. Patients who are intolerant of, or have refused treatment with standard first line cancer therapy, will be allowed to enroll. Patients must not have had more than 5 prior systemic regimens (excluding experimental therapies) for unresectable locally advanced or metastatic disease.
  • B7-H3 expression is not required for eligibility in this study; however, tumor expression of B7-H3 will be evaluated for all patients.
  • Measurable disease per RECIST 1.1 criteria
  • ECOG performance status 0 or 1
  • Acceptable laboratory parameters and adequate organ reserve.

Exclusion Criteria - Cohort Expansion Phase:

  • Patients with a history of symptomatic central nervous system metastases, unless treated and asymptomatic
  • Patients with history of autoimmune disease with certain exceptions
  • History of allogeneic bone marrow, stem cell, or solid organ transplant
  • Treatment with systemic cancer therapy or investigational therapy within 4 weeks; radiation within 2 weeks; trauma or major surgery within 4 weeks
  • History of clinically-significant cardiovascular disease; gastrointestinal perforation; gastrointestinal bleeding, acute pancreatitis or diverticulitis within 4 weeks;
  • Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days; positive for human immunodeficiency virus or AIDS, hepatitis B or C.
  • Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient contained in the drug or vehicle formulation for MGA271 or ipilimumab.

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): NCT02381314


Locations
United States, California
UCLA Hematology-Oncology Clinic
Los Angeles, California, United States, 90095
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Florida
Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Missouri
Washington University School of Medicine in St. Louis
Saint Louis, Missouri, United States, 63110
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Texas
Center for Oncology and Blood Disorders
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
MacroGenics
Investigators
Study Director: James Vasselli, M.D. MacroGenics

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT02381314     History of Changes
Other Study ID Numbers: CP-MGA271-02
First Posted: March 6, 2015    Key Record Dates
Last Update Posted: March 6, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by MacroGenics:
Other B7-H3 expressing cancers

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Melanoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs