This phase I trial tests the safety, side effects, and best dose of TAG72-chimeric antigen receptor (CAR) T cells in treating patients with epithelial ovarian cancer that remains despite treatment with platinum therapy (platinum resistant). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize TAG72, a protein on the surface of tumor cells. These TAG72-specific T cells may help the body's immune system identify and kill TAG72+ cancer cells.
Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable exceptions may be granted with Study PI approval.
Age > 18 years.
ECOG Performance status 0 - 2 or KPS ≥70%.
Documented platinum resistant EOC (defined as disease that has progressed within six months of completing platinum therapy, or lack of response or disease progression while receiving the most recent platinum-based therapy, respectively). Progression may be determined radiographically (not RECIST) or by new onset of malignant pleural effusion. Participant may have at least 1 measurable lesion or disease measured by PCI at the time of surgery.
Participant has not yet recovered from toxicities of prior therapy.
Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
History of allergic reactions attributed to compounds of similar chemical or biologic composition or other agents used in this study.
History of (non-infectious or COVID-related) pneumonitis that required steroids or current pneumonitis
Single group
Chimeric Antigen Receptor T-cells
Biological/VaccineReceive TAG72-CAR T cells IP
Cyclophosphamide
DrugGiven IV
Fludarabine
DrugGiven IV
Incidence of dose limiting toxicities (DLTs)
Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated.
Incidence of adverse events
Adverse Events are graded using NCI CTCAE v.5.
Persistence of CAR T cells
Defined as CAR T cells \> 0.1% of total CD3 cells by flow-cytometry.
Expansion of CAR T cells
Max log10 copies/ug of genomic DNA
Response (iRECIST)
Assessed based on Immune-Related Response Criteria. Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated.
Overall survival (OS)
Defined as death from all causes from first treatment date (either lymphodepletion or CAR T cell infusion, as applicable. Kaplan Meier methods will be used to estimate median OS, and graph the results.
Phenotypes and frequencies of immune cell subsets in the peripheral bloodpre- 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. Will provide descriptive statistics for exploratory studies. Data will be presented as % of total cells, or as cell/mL blood or peritoneal fluid.
Phenotype of tumor-infiltrating lymphocytes
Will provide descriptive statistics for exploratory studies.
Gene expression
Assessed by ribonucleic acid sequencing (RNA-seq) of circulating tumor cells (CTCs). Will provide descriptive statistics for exploratory studies.
Circulating cell-free deoxyribonucleic acid in peripheral blood
Assessed by whole exome sequencing.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
