On December 21, 2020 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, and City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases, reported that a Phase 1 single-center, two-arm clinical trial has been initiated to establish the safety and feasibility of administering MB-101 (autologous IL13Rα2-CAR T cells) to patients with leptomeningeal brain tumors (e.g., glioblastoma, ependymoma or medulloblastoma) (Press release, Mustang Bio, DEC 21, 2020, View Source [SID1234573176]). The trial will enroll up to 30 patients and take place at City of Hope, where the chimeric antigen receptor T ("CAR T") cell therapy was initially developed.
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All subjects enrolled in the trial will undergo surgery for the placement of an intraventricular (ICV) Rickham catheter for CAR T cell delivery. The Phase 1 trial will establish the safety and feasibility of administering MB-101 through the ICV Rickham catheter over four weekly cycles in patients with glioblastoma (Arm 1) and ependymoma or medulloblastoma (Arm 2). The primary endpoints that will be evaluated are toxicity and survival at three months. Secondary endpoints include overall survival, CAR T and endogenous T cell levels, cytokine levels and phenotype detection in peripheral blood, tumor cyst fluid and cerebrospinal fluid.
Lisa Feldman, M.D., Ph.D., a neurosurgeon and assistant clinical professor in the Division of Neurosurgery at City of Hope and principal investigator of the clinical trial, commented, "Leptomeningeal brain tumors are a form of metastatic brain cancer, which is currently very difficult to treat. We are encouraged by the potential of administering autologous IL13Rα2-CAR T cells intraventricularly to patients with leptomeningeal brain tumors. This CAR T cell therapy has demonstrated early safety and efficacy results in a previous clinical trial conducted at City of Hope, and we believe these preliminary results warrant further evaluation of these CAR T cells. We look forward to providing updates on the trial and to continue working closely with Mustang with the goal of bringing a safe and effective treatment option to patients with this life-threatening disease."
Manuel Litchman, M.D., president and chief executive officer of Mustang, said, "We are pleased to further study MB-101 in leptomeningeal brain tumors as it has already demonstrated therapeutic potential when infused into the ventricular system, including delivering a complete response in a leptomeningeal glioblastoma patient that was published in the New England Journal of Medicine. Our ongoing work with City of Hope continues to advance the research of our CAR T portfolio to bring potential therapies to patients suffering from devastating diseases."
Additional information about the trial can be found on clinicaltrials.gov using the identifier NCT04661384.
About MB‐101 (IL13Rα2‐specific CAR T cells)
IL13Rα2 is an attractive target for CAR T therapy as it has limited expression in normal tissue but is overexpressed on the surface of the majority of malignant glioma cells, including glioblastoma multiforme, ependymoma and medulloblastoma. CAR T cells are designed to express a membrane‐tethered IL‐13 receptor ligand (IL‐13) incorporating a single‐point mutation that provides high affinity for IL13Rα2 and reduces binding to IL13Rα1 in order to reduce healthy tissue targeting. Mustang is developing MB‐101 as an optimized CAR T product incorporating enhancements in CAR design and T cell engineering to improve antitumor potency and T cell persistence. MB‐101 includes a second‐generation hinge optimized CAR containing mutations in the IgG4 linker to reduce off‐target Fc interactions, the 4-1BB (CD137) co‐stimulatory signaling domain for improved persistence of CAR T cells and the extracellular domain of CD19 as a selection/safety marker. To further improve persistence, central memory T cells are enriched and genetically engineered using a manufacturing process that limits ex vivo expansion to reduce T cell exhaustion and maintain a memory T cell phenotype.