Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
CP-MGA271-02
- NCT ID:
NCT02381314
Conditions
- Melanoma
- Non Small Cell Lung Cancer
Interventions
Drug | Synonyms | Arms |
---|
enoblituzumab plus ipilimumab | enoblituzumab (MGA271); ipilimumab (Yervoy) | enoblituzumab plus ipilimumab |
Purpose
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).
Trial Arms
Name | Type | Description | Interventions |
---|
enoblituzumab plus ipilimumab | Experimental | 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. | - enoblituzumab plus ipilimumab
|
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with adverse events |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Adverse events, serious adverse events |
Secondary Outcome Measures
Measure: | Peak plasma concentration |
Time Frame: | 7 weeks |
Safety Issue: | |
Description: | PK of MGA271 in combination with ipilimumab |
Measure: | Number of participants that develop anti-drug antibodies |
Time Frame: | 7 weeks |
Safety Issue: | |
Description: | Proportion of patients who develop anti-MGA271 antibodies, immunogenicity |
Measure: | Change in tumor volume |
Time Frame: | Weeks 9, 18, 27, 39, and 51 |
Safety Issue: | |
Description: | Anti-tumor activity of MGA271 in combination with ipilimumab using both conventional RECIST 1.1 and immune-related RECIST criteria. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | MacroGenics |
Trial Keywords
- Other B7-H3 expressing cancers
Last Updated
March 25, 2019