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

Melanoma Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02381314
• Other study ID #: CP-MGA271-02
• Status: Completed
• Phase: Phase 1
• Start date: March 26, 2015
• Est. completion date: September 26, 2018

Study information

• Verified date: February 2022
• Source: MacroGenics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 26, 2018
• Est. primary completion date: November 9, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Melanoma
• Non Small Cell Lung Cancer

Intervention

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.

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois
United States	Center for Oncology and Blood Disorders	Houston	Texas
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	UCLA Hematology-Oncology Clinic	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Yale University	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Providence Portland Medical Center	Portland	Oregon
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events	Adverse events, serious adverse events	1 year
Secondary	Peak plasma concentration	PK of MGA271 in combination with ipilimumab	7 weeks
Secondary	Number of participants that develop anti-drug antibodies	Proportion of patients who develop anti-MGA271 antibodies, immunogenicity	7 weeks
Secondary	Change in tumor volume	Anti-tumor activity of MGA271 in combination with ipilimumab using both conventional RECIST 1.1 and immune-related RECIST criteria.	Weeks 9, 18, 27, 39, and 51