HER2-CAR T Cells in Treating Patients With Recurrent Brain or Leptomeningeal Metastases

PRIMARY OBJECTIVES: I. Determine the safety and recommended phase 2 dosing (RP2D) of intraventricularly administered memory-enriched autologous HER2(EQ)BBzeta/CD19t+ T cells (HER2-chimeric antigen receptor \[CAR\] T cells) - either HER2(EQ)BBzeta/CD19t+ TCM in Arm 1, or HER2(EQ)BBzeta/CD19t+ TN/MEM in Arm 2 - in participants with brain and/or leptomeningeal metastases from HER2 positive cancers. SECONDARY OBJECTIVES: I. Assess cerebrospinal fluid (CSF) and peripheral blood for HER2-CAR T cell persistence and endogenous immune system activation. II. Describe changes in cytokine levels in the CSF and peripheral blood. III. Describe changes in circulating tumor cells in the CSF. IV. In study participants who complete at least the first three cycles of HER2-CAR T cell infusions: IVa. Describe the CNS clinical benefit defined as disease response rate based on Response Assessment in Neuro-Oncology Criteria (RANO) criteria (stable disease \[SD\], partial response \[PR\], or complete response \[CR\] in the brain). IVb. Describe the systemic clinical benefit based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria. IVc. Estimate the median central nervous system (CNS) progression-free and overall survival rates (mPFS and mOS), (newly diagnosed versus recurrent metastases). V. In study participants who undergo tumor resection or biopsy during or after study treatment or upon autopsy, evaluate the tumor micro-environment for: Va. HER2-CAR T cell persistence. Vb. Immune cell subsets. Vc. Cytokine levels. Vd. HER2 antigen expression levels. VI. Use biomathematical modeling of tumor growth to evaluate benefit of treatment. OUTLINE: This is a dose-escalation study. Patients receive HER2-CAR T cells via intraventricular administration over 5 minutes once weekly for 3 doses in the absence of disease progression or unacceptable toxicity. If patients continue to meet all eligibility criteria, they may receive additional cycles of HER2-CAR T cells at principal investigator's discretion. After completion of study treatment, participants are followed up at 4 weeks, 3, 6, 8, 10, and 12 months, and then for up to 15 years.