Safety/Feasibility of CAR T-Cell Therapy Being Investigated in Brain Tumors

Sara Karlovitch

Sara Karlovitch is an associate editor with Targeted Oncology. She received a duel degree in Journalism and Government and Politics from the University of Maryland.

The first patient has been dosed in a study designed to evaluate the safety and feasibility of IL13Rα2 chimeric antigen receptor T cell therapy for the treatment of leptomeningeal brain tumors, such as glioblastoma, ependymoma, and medulloblastoma.

The first patient has been dosed in a study (NCT04661384) designed to evaluate the safety and feasibility of IL13Rα2 chimeric antigen receptor (CAR) T cell therapy (MB-101) for the treatment of leptomeningeal brain tumors, such as glioblastoma, ependymoma, and medulloblastoma, according to a press release by MustangBio.

IL13Rα2 is often overexpressed on the surface of the majority of malignant glioma cells but has limited expression in normal tissue, making it an ideal target for CAR T-cell therapy. They therapy is meant to express a membrane-tethered IL-13 receptor ligand which incorporates a single-point mutation that reduces binding to IL13Rα2 to reduce the targeting of health tissue. Additionally, the CAR T-cell therapy is being engineered to enhance antitumor potency and T cell persistence.

The single-arm study is being conducted at the City of Hope Comprehensive Cancer Center. The study has an estimated enrollment of 30 participants and primary endpoints of incidence of adverse events up to 15 years and overall survival at 3 months. Secondary outcomes include CAR T-cell levels, endogenous T-cell levels detected in tumor cyst fluid, cell phenotype detected in tumor cyst fluid, cytokine levels, time to progression, overall survival, IL13Rα2 antigen expression in tumor tissue, biomathematical modeling of tumor growth, and biomathematical modeling of perfusion/diffusion.

During the trial, patients will undergo surgery in order to place an intraventricular Rickham catheter for CAR T-cell delivery. Patients will then receive the CAR T cells over the course of 5 minutes on day 1. The treatment will repeat every 7 days for 4 cycles in the absence of disease progression or until unacceptable toxicity.

In order to participate, patients must have treated leptomeningeal metastases after intrathecal chemotherapy and/or radiation or refuses to under radiation and/or intrathecal chemotherapy. Additionally, patients must have a Karnofsky performance status equal to or greater than 60 and a life expectancy of 8 weeks or more. Patients who require supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks, require dialysis, uncontrolled seizure activity, or are unwilling to stop treatment with chemotherapy or endocrine therapy, are not eligible to participate.

“Based on our research to date, including a previous clinical trial at City of Hope, further evaluation is warranted for this CAR T-cell therapy. The prior clinical trial demonstrated encouraging potential of administering autologous IL13Rα2-CAR T cells intraventricularly to help treat patients with leptomeningeal brain tumors, a form of metastatic brain cancer that is difficult to treat. We continue to work closely with the Mustang team to potentially bring a safe, effective treatment option to patients suffering with this life-threatening disease,” said Lisa Feldman, MD, PhD, a neurosurgeon and assistant clinical professor in the Division of Neurosurgery at City of Hope and the study’s principle investigator in a press release.

The FDA has granted approvals to numerous CAR T cell therapies for relapsed or refractory (R/R) multiple myeloma, R/R large B-cell lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma. Efforts to use CAR T cells for the treatment of solid tumors has been met with limited success.

“The successful dosing of the first patient in this clinical trial of MB-101 is an important milestone in Mustang’s development program. We are pleased to support City of Hope to further study MB-101 in leptomeningeal brain tumors to potentially bring hope to patients suffering from this devastating and fatal disease,” said Manuel Litchman, MD, president and CEO of MustangBio in a press release. “MB-101 has already demonstrated therapeutic potential when infused into the ventricular system, including delivering a complete response in a patient with leptomeningeal glioblastoma that was published in the New England Journal of Medicine. We aim to generate additional data that supports the advancement of this program.”

REFERENCE:
Mustang Bio and City of Hope announce first patient dosed in phase 1 clinical trial of MB-101 (IL13Rα2-specific CAR T cells) to treat leptomeningeal brain tumors. News Release. MustangBio. May 18, 2021. Accessed May 18, 2021. https://bit.ly/3bzihQv.