Modified Immune Cells (TAG72-CAR T Cells) for the Treatment of Patients With Platinum Resistant Epithelial Ovarian Cancer

PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of TAG72-CAR T cells in participants with recurrent epithelial ovarian cancer (EOC). II To determine the maximum tolerated dose (MTD). III. To identify the recommended phase 2 dose (RP2D). SECONDARY OBJECTIVES: I. Persistence of CAR T cells in blood and peritoneal cavity pre- and 28 days post-infusion. II. Response based on Immune-Related Response Criteria (irRC). III. Estimate the 6 month progression free survival rate. IV. Estimate median overall survival. V. TAG72 expression on tumor cells by immunohistochemistry (IHC) and/or flow cytometry; VI. Describe the serum cytokine profile pre- and post-CAR T cell infusion to assess potential cytokine release syndrome (CRS) toxicity and CAR T cell effector function. EXPLORATORY OBJECTIVES: I. Phenotypes and frequencies of immune cell subsets in the peripheral blood pre- and post- therapy: analysis will include CD4:CD8 ratios, differentiation status (CD62L, CD27, CD45 RA/RO), and exhaustion markers (PD1, Tim3, LAG3), trafficking (CCR7, alpha4beta7), proliferation markers (ki67) and effector functions (cytotoxicity, Th1/Th2 cytokines, and CD107a degranulation) on endogenous and CAR+ T cells. II. Phenotype of tumor-infiltrating lymphocytes (TILs). III. Gene expression (by RNA-seq) of circulating tumor cells (CTCs). IV. Circulating cell-free deoxyribonucleic acid (cfDNA) in peripheral blood by whole exome sequencing. V. CAR immunogenicity based on the presence of anti-TAG72 CAR antibodies or T cell mediated immune responses. OUTLINE: This is a dose-escalation study of TAG72-CAR T cells. Patients receive fludarabine intravenously (IV) and cyclophosphamide IV on days -5 to -3. Patients receive TAG72-CAR T cells IP on day 0. After completion of study treatment, patients are followed up at 1, 7, 14, 21, 28, 60 and 90 days, 6, 9, and 12 months, then for up to 15 years.