Clinical trial NCT02381314: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Non Small Cell Lung Cancer
Keywords: Other B7-H3 expressing cancers
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
First posted: 2015-03-06
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: 1 year
Secondary outcomes:
measure: Peak plasma concentration
timeFrame: 7 weeks
measure: Number of participants that develop anti-drug antibodies
timeFrame: 7 weeks
measure: Change in tumor volume
timeFrame: Weeks 9, 18, 27, 39, and 51
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Hematology-Oncology Clinic
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Houston
country: United States
facility: Center for Oncology and Blood Disorders
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: MacroGenics
name: Chief Medical Officer
role: STUDY_DIRECTOR
References: