IL-8 Receptor Modified Patient-Derived Activated CD70 CAR T Cell Therapy in Adults With Brain Metastases

Adult patients with newly diagnosed or recurrent/progressive brain metastases will be screened. Consented patients will undergo screening procedures followed by tumor biopsy/surgery if clinically indicated, and may receive treatment for brain metastases, which include whole brain radiation therapy (WBRT), SRS treatment for new lesion(s) (SRS is permitted for recurrent disease only for newly developed brain lesion(s). Enrollment and administration of standard-of-care treatment will be coordinated such that each subject will not receive the CAR T-cell product until the preceding subject has completed the required 28-day dose-limiting toxicity observation period.

After enrollment, patients will be evaluated for cellular therapy suitability and undergo cell collection for the generation of 8R-70CAR T cells before initiation or up to two cycles while receiving standard-of-care chemoradiation. As part of screening, CD70 protein will be confirmed on primary tumor or lymph nodes biopsy. If the patient is eligible, they will receive FDA-approved standard of care therapy for their primary disease as a 2-4 cycles bridge while the 8R-70 CAR T cells are being manufactured. Following completion of standard of care therapy and prior to cellular therapy, patients will be evaluated to confirm disease stability. MRI of brain and CT imaging will be obtained within 28 days prior to CAR administration for disease staging.

If radiographic or clinical progression is identified, the treating physicians may consider initiating therapy for the primary disease prior to CAR administration. Upon completion of the additional line of therapy, eligibility for CAR administration will be reassessed at the discretion of the treating physicians based on overall clinical stability and disease control.

A single dose of 8R-70CAR T cells will be administered IV injection 2 to 6 months after study enrollment. Administration will be conducted in the hospital so the patient can be monitored for infusion-related toxicities.

After hospital discharge, patients will be required to remain within a 1-hour drive of UF Health for at least two weeks following infusion for safety monitoring. Patients receiving study treatment will be required to have a caregiver and advised to avoid driving for two weeks following product administration.

Patients will have post-infusion follow-up visits in the UF Health clinic 7 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, and 12 weeks after CAR T administration.

Patients who continue to receive care at the University of Florida will be seen at the UF Health Neuro-oncology/Neurosurgery clinic every 2 months, for the first 12-24 months, then every 3 months for 12 months, then every 4 months or when clinically indicated for physical \& neuro exam, interim medical history, until progressive disease and every 6 months thereafter.

Patients who transfer their care to an outside provider/institution will be contacted by phone at 3, 6, 12 months, and every 6 months thereafter for follow-up.

All patients who receive the 8R-70 CAR T cells investigational product will continue to be followed until death. Patients will also be followed up to 15 years in accordance with the guidance "Gene Therapy Clinical Trials - Observing Subjects for Adverse Events" to identify and mitigate the potential long-term risks to the patients receiving the investigational product.