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

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma; Non Small Cell Lung Cancer
• Intervention / Treatment: Biological: enoblituzumab plus 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).

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: enoblituzumab (MGA271); ipilimumab (Yervoy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	Adverse events, serious adverse events	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration	PK of MGA271 in combination with ipilimumab	7 weeks
Number of participants that develop anti-drug antibodies	Proportion of patients who develop anti-MGA271 antibodies, immunogenicity	7 weeks
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

Collaborators and Investigators

• Sponsor: MacroGenics

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2015
• Primary Completion (Actual): November 9, 2017
• Study Completion (Actual): September 26, 2018

Study Registration Dates

• First Submitted: February 20, 2015
• First Submitted That Met QC Criteria: March 2, 2015
• First Posted (Estimate): March 6, 2015

Study Record Updates

• Last Update Posted (Actual): February 8, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Other B7-H3 expressing cancers
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab
• Other Study ID Numbers: CP-MGA271-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED