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

This is an interventional treatment trial for Platinum-Resistant Ovarian Carcinoma Read More

Inclusion Criteria:

• Participant must have the ability to understand and the willingness to sign a written informed consent

  • Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed. However, the research participant can proceed with lymphodepletion (if applicable) and CAR T cell infusion only after the translated full consent form is signed
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable exceptions may be granted with study principal investigator (PI) approval
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 or Karnofsky performance status (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 must be determined radiographically. Participant must have at least 1 measurable lesion
• 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 agents if, in the investigator's opinion, they would benefit from treatment on the current protocol

  • Participants with known germline or somatic BRCA mutation, HRD positive disease or history of platinum sensitive recurrence before developing platinum resistant EOC, must also have received niraparib, Olaparib, rucaparib or other approved PARP inhibitors. (Platinum sensitivity is defined as disease progression occurring greater than 6 months of completing last platinum therapy).
• 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
• Total serum bilirubin =< 2.0 mg/dL (performed within 42 days of signing the screening and leukapheresis consent) Patients with Gilbert syndrome may be included if their
• total bilirubin is < 3.0 x upper limit of normal (ULN) and direct bilirubin =< 1.5 x ULN
• Aspartate aminotransferase (AST) =< 5 x ULN (performed within 42 days of signing the screening and leukapheresis consent)
• Alanine aminotransferase (ALT) =< 5 x ULN (performed within 42 days of signing the screening and leukapheresis consent)
• Coagulation Parameters: Participants not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5xULN
• Creatinine clearance of >= 50 mL/min per the Cockcroft-Gault formula (performed within 42 days of signing the screening and leukapheresis consent)
• Cardiac function (12 lead-electrocardiogram [ECG]) without acute abnormalities requiring investigation or intervention (performed within 42 days of signing the screening and leukapheresis consent)
• Left ventricular ejection fraction > 40% (performed within 42 days of signing the screening and leukapheresis consent)

Exclusion Criteria:

• Participants with the following histologies should be excluded:
• Low-grade serous carcinoma
• Mucinous carcinoma
• Carcinosarcoma
• Participant has not yet recovered from toxicities of prior therapy
• Participant with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of signing the screening and leukapheresis consent
• Participant with known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder
• Active autoimmune disease requiring systemic immunosuppressive therapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition or other agents used in this study
• Current signs and/or symptoms of bowel obstruction
• History of inflammatory bowel disease
• History of gastrointestinal perforation or symptomatic diverticular disease confirmed by CT or colonoscopy
• History of intra-abdominal abscess within the past 3 months.
• Patients with known peritoneal adhesions that preclude the placement of an intraperitoneal catheter in the opinion of the surgeon placing the intraperitoneal catheter.
• Participant with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of signing the screening and leukapheresis consent.
• Participant with known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder.
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia, and participants on therapeutic anti-coagulation.
• History of stroke or intracranial hemorrhage within 6 months prior to signing the screening and leukapheresis consent
• History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent with no known active disease present for >= 3 years, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
• Uncontrolled active infection
• Active hepatitis B or hepatitis C infection
• Human immunodeficiency virus (HIV) infection
• Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures.
• Massive ascites requiring therapeutic paracentesis will not be cause for ineligibility, per se, but will be evaluated on an individual basis. Investigators who have questions regarding assessing ascites are asked to speak with the Principal Investigator.
• Prospective participants who, in the opinion of the Investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)