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

• Status: Not yet recruiting
• Trial end date: 2024-12-30
• Target enrollment: 0
• Participant gender: Female

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: City of Hope Medical Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cyclophosphamide; Fludarabine

Criteria

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

• 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)

• 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:

• Owing to higher frequency of wound-related complications, participants who within 3 months of having received prior bevacizumab therapy at the time of enrollment are excluded

• 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

• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia

• 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

• 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)