Safety Study of Enoblituzumab (MGA271) in Combination With Ipilimumab in Refractory Cancer
Primary Purpose
Melanoma, Non Small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
enoblituzumab plus ipilimumab
Sponsored by

About this trial
This is an interventional treatment trial for Melanoma focused on measuring Other B7-H3 expressing cancers
Eligibility 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.
Sites / Locations
- UCLA Hematology-Oncology Clinic
- Yale University
- Mount Sinai Medical Center
- University of Chicago
- Indiana University Simon Cancer Center
- Washington University School of Medicine in St. Louis
- Columbia University Medical Center
- Providence Portland Medical Center
- Center for Oncology and Blood Disorders
- University of Wisconsin
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
enoblituzumab plus ipilimumab
Arm Description
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.
Outcomes
Primary Outcome Measures
Number of participants with adverse events
Adverse events, serious adverse events
Secondary Outcome Measures
Peak plasma concentration
PK of MGA271 in combination with ipilimumab
Number of participants that develop anti-drug antibodies
Proportion of patients who develop anti-MGA271 antibodies, immunogenicity
Change in tumor volume
Anti-tumor activity of MGA271 in combination with ipilimumab using both conventional RECIST 1.1 and immune-related RECIST criteria.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02381314
Brief Title
Safety Study of Enoblituzumab (MGA271) in Combination With Ipilimumab in Refractory Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
March 26, 2015 (Actual)
Primary Completion Date
November 9, 2017 (Actual)
Study Completion Date
September 26, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MacroGenics
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma, Non Small Cell Lung Cancer
Keywords
Other B7-H3 expressing cancers
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
enoblituzumab plus ipilimumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
enoblituzumab plus ipilimumab
Other Intervention Name(s)
enoblituzumab (MGA271); ipilimumab (Yervoy)
Intervention Description
enoblituzumab is administered by IV infusion once per week. Ipilimumab is administered by IV infusion every 3 weeks for up to 4 doses.
Primary Outcome Measure Information:
Title
Number of participants with adverse events
Description
Adverse events, serious adverse events
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Peak plasma concentration
Description
PK of MGA271 in combination with ipilimumab
Time Frame
7 weeks
Title
Number of participants that develop anti-drug antibodies
Description
Proportion of patients who develop anti-MGA271 antibodies, immunogenicity
Time Frame
7 weeks
Title
Change in tumor volume
Description
Anti-tumor activity of MGA271 in combination with ipilimumab using both conventional RECIST 1.1 and immune-related RECIST criteria.
Time Frame
Weeks 9, 18, 27, 39, and 51
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chief Medical Officer
Organizational Affiliation
MacroGenics
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Hematology-Oncology Clinic
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Mount Sinai Medical Center
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana University Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Washington University School of Medicine in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Providence Portland Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
Center for Oncology and Blood Disorders
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Safety Study of Enoblituzumab (MGA271) in Combination With Ipilimumab in Refractory Cancer
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