City of Hope has opened a first-in-human clinical trial for patients with recurrent glioblastoma. The trial is the first to combine City of Hope’s chimeric antigen receptor (CAR) T cells that target the IL13Rα2 antigen common on brain tumor cells in combination with nivolumab and ipilimumab.
Behnam Badie, MD
Christine Brown, PhD
To launch the randomized trial, the National Institutes of Health awarded $3.3 million over 5 years to Behnam Badie, MD, Heritage Provider Network Professor in Gene Therapy and Chief of Neurosurgery, and Christine Brown, PhD, Heritage Provider Network Professor in Immunotherapy and Deputy Director of the T-Cell Therapeutics Research Laboratory, both at City of Hope. Drs. Badie and Brown also received $800,000 from Gateway for Cancer Research.
The trial will deliver CAR T cells that target IL13Rα2 locally to the brain, by direct injection to the tumor site and through infusion into the ventricular system. All patients will receive the IL13Rα2 CAR T cells weekly, combined with nivolumab every other week. Patients on the experimental arm will additionally receive ipilimumab and nivolumab, each dosed once, 14 days prior to the start of combination therapy with CAR T cells plus nivolumab.
City of Hope was the first to use this type of delivery for patients with glioblastoma receiving CAR T-cell treatment, as well as the first to investigate CAR T cells targeting IL13Rα2. A 2016 case study published in TheNew England Journal of Medicine outlined how a City of Hope patient’s brain cancer regressed for 7.5 months after receiving CAR T-cell therapy to effectively attack cells with IL13Rα2.1
The U.S. Food and Drug Administration (FDA) has approved the use of nivolumab for patients with various cancers, including metastatic melanoma, non–small cell lung cancer, classical Hodgkin lymphoma, and head and neck cancer. Clinical trials are underway at City of Hope and other institutions to expand the use of nivolumab for other cancers and for use with other therapies. The FDA has approved the use of ipilimumab for metastatic melanoma or in combination with nivolumab for renal cell carcinoma and colorectal cancer. ■
1. Brown CE, Alizadeh D, Starr R, et al: Regression of glioblastoma after chimeric antigen receptor T-cell therapy. N Engl J Med 375:2561-2569, 2016.