A Phase 1 Study to Evaluate TAG72-Targeting Chimeric Antigen Receptor (CAR) T Cells in Patients With Advanced Epithelial Ovarian Cancer
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.
• Participant must have the ability to understand and the willingness to sign a written informed consent.
• 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.
• Documented TAG72+ (\> 1% cells ≥ +1 intensity) tumor expression by IHC (MAb CC49) as evaluated by COH Pathology Core.
• In addition to platinum agents, participant must have received and failed, or have been intolerant to taxanes, liposomal doxorubicin or other agents known to confer clinical benefit. Participants are not required to fail all of these chemotherapy agents if, in the investigator's opinion, they would benefit from treatment on the current protocol.
• No known contraindications to leukapheresis, steroids or tocilizumab.
• Participant of reproductive potential must agree to use acceptable birth control methods throughout study therapy and for 3 months after final dose of study treatment.
• \_ANC ≥ 1,000/mm3
• Total serum bilirubin ≤ 1.5 x ULN Patients with Gilbert syndrome may be included if their total bilirubin is \< 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN.
• AST \< 3 x ULN if liver metastasis: AST \< 5 x ULN)
• ALT \< 3 x ULN if liver metastasis: ALT \< 5 x ULN)
• Participants not receiving therapeutic anticoagulation: INR or aPTT ≤1.5 x ULN
• Creatinine clearance of ≥ 50 mL/min per the Cockcroft-Gault formula
• Cardiac function (12 lead-ECG) without acute abnormalities requiring investigation or intervention
• Left ventricular ejection fraction \>40%
• QuantiFERON-TB Gold or equivalent\*