Testing CAR-T Cell Therapy in Recurrent Epithelial Ovarian Cancer

Inclusion Criteria

• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. Subjects or their Legally Authorized Representative must sign a consent to undergo cell procurement. Subject will be given a copy of the informed consent form
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Age >= 18 years at the time of consent
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject has adequate performance status as defined by Eastern Cooperative Oncology Group (ECOG) score of =< 2
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subjects must have histologically or cytologically confirmed epithelial ovarian, peritoneal or fallopian tube cancer and must have a histological diagnosis of a high-grade serous histology based on local histopathological findings
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subjects must have recurrent platinum-resistant or platinum-refractory disease defined as: * Disease that has progressed by imaging while receiving platinum OR * Disease that has recurred within 6 months of the last receipt of platinum-based chemotherapy. Rising CA-125 only is not considered as platinum-resistant or refractory disease * Having received at least 2 prior regimens * Have failed prior therapy with a PARP inhibitor if the subject has a germline or somatic BRCA mutation
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subjects must have evaluable disease – defined as: * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 OR * Non-measurable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions) OR * Ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related in the setting of a CA-125 > 2 x upper limit of normal (ULN)
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subjects must be able to have an intraperitoneal port placed either by vascular interventional radiology or surgically in the operating room. (Note: The intraperitoneal port will not be placed until the subject is determined to be otherwise eligible to receive the CAR.B7-H3 infusion and until the subject is determined to be otherwise eligible to receive lymphodepletion)
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of highly effective methods of contraception from the time of informed consent until 180 days after study treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets < 1% failure rate for protection from pregnancy in the product label
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject is willing and able to comply with study procedures based on the judgement of the investigator
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject is willing to undergo a biopsy prior to treatment, at the time of intraperitoneal catheter removal, and at the time of disease progression (if not at their first scan), and the tumor site is determined to be safe by the treating investigator for biopsy collection
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study)
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject is deemed unlikely to be a candidate for successful intraperitoneal catheter placement by radiographic assessment
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject has intraparenchymal lung metastases (note that pleural effusions are not exclusionary and that subjects with intraparenchymal liver disease and subjects with retroperitoneal disease are allowed on the study)
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject has brain metastases. A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to being screened for eligibility, have been off of corticosteroids for >= 2 weeks, and are asymptomatic
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject has current signs and/or symptoms of bowel obstruction or signs and/or symptoms of a bowel obstruction within 3 months prior to starting treatment
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject has a history of intra-abdominal abscess within the past 3 months
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject has a history of gastrointestinal perforation
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject has a history of symptomatic diverticular disease, confirmed by computed tomography (CT) or colonoscopy
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject is dependent on intravenous hydration or total parenteral nutrition
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject must not be currently using systemic corticosteroids at doses >=10 mg prednisone daily or its equivalent; those receiving < 10 mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed. Physiologic replacement hydrocortisone at doses 6-12 mg/m^2/day is allowed. Equivalently dosed alternative steroids are allowed at discretion of investigator, though not to exceed 10 mg prednisone per day
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject has active infection with human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV) (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells). Note: To meet eligibility subjects are required to be negative for HIV antibody or HIV viral load, negative for HTLV1 and 2 antibody or polymerase chain reaction (PCR) negative for HTLV1 and 2, negative for hepatitis B surface antigen, negative for HCV antibody or HCV viral load
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subjects must not have a history of intolerance to fludarabine
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subject has life expectancy >= 3 months
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Total bilirubin =< 1.5 x ULN, unless attributed to Gilbert’s syndrome
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 3 x ULN (Note: if intrahepatic liver metastases are present, AST and ALT must be =< 5 x ULN)
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Creatinine =< 2 x ULN
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Left ventricular ejection fraction (LVEF) >= 40%, as measured by echocardiography (ECHO), with no additional evidence of decompensated heart failure
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Pulse oximetry >= 90% on room air
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Subjects must have active disease by imaging assessment within 90 days prior to procurement
• ELIGIBILITY CRITERIA PRIOR TO CELL PROCUREMENT: Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to cell procurement. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Written informed consent explained to, understood by and signed by the subject prior to lymphodepletion; subject given a copy of informed consent form
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject has an intraperitoneal catheter/port in place. (Note: The intraperitoneal port will not be placed until the subject is determined to be otherwise eligible to receive lymphodepletion prior to the CAR.B7-H3 infusion)
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject had no major surgery within 28 days prior to lymphodepletion
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject has not received any investigational agents or any tumor vaccines within 21 days prior to lymphodepletion
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subjects must have stopped systemic chemotherapy or radiation therapy for at least 21 days prior to lymphodepletion
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject must have stopped bevacizumab for at least 6 weeks prior to lymphodepletion
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject must have stopped hormonal therapy (tamoxifen, letrozole, etc.) for at least 21 days prior to lymphodepletion
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject is not receiving a prohibited medication at the time of starting lymphodepletion up through 72 hours after the last dose of cyclophosphamide
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: No current use of systemic corticosteroids at doses >= 10 mg prednisone daily or its equivalent; those receiving < 10 mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed. Physiologic replacement hydrocortisone at doses 6-12 mg/m2/day is allowed. Equivalently dosed alternative steroids are allowed at discretion of investigator, though not to exceed 10 mg prednisone per day
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Imaging results from within 10 days prior to lymphodepletion. Imaging must occur at least 3 weeks after most recent therapy (used as baseline measure for documentation of progression before the lymphodepletion) to document measurable or assessable disease. Imaging does not need to be repeated if it is within 10 days prior to lymphodepletion. Subjects must have evaluable disease defined as: * Measurable disease per RECIST 1.1 OR * Non-measurable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions) OR * Ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related in the setting of a CA-125 > 2 × ULN
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Hemoglobin >= 8 g/dL (within 48 hours prior to lymphodepletion)
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Absolute neutrophil count >= 1.0 x 10^9/L (within 48 hours prior to lymphodepletion)
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Platelet count >= 100 x 10^9/L (within 48 hours prior to lymphodepletion)
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Total bilirubin =< 1.5 x ULN, unless attributed to Gilbert’s syndrome (within 48 hours prior to lymphodepletion)
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: AST / ALT =< 3 x ULN (Note: if intrahepatic liver metastases are present, AST and ALT must be =< 5 x ULN) (within 48 hours prior to lymphodepletion)
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Creatinine =< 2 x ULN (within 48 hours prior to lymphodepletion)
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject does not have intraparenchymal lung metastases (Note: Pleural effusions are not exclusionary and that subjects with intraparenchymal liver disease and subjects with retroperitoneal disease are allowed on the study)
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject does not have a known brain metastasis. A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to lymphodepletion, have been off corticosteroids for > 2 weeks, and are asymptomatic
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject must have available autologous transduced activated T cells product that meets the Certificate of Analysis acceptance
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject does not have current signs and/or symptoms of bowel obstruction or signs and/or symptoms of a bowel obstruction within the last 3 months prior to lymphodepletion
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject does not have a history of gastrointestinal perforation
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject does not have a history of intra-abdominal abscess within 3 months of lymphodepletion
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject does not have a history of symptomatic diverticular disease, confirmed by CT or colonoscopy
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject is not dependent on intravenous hydration or total parenteral nutrition
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Negative serum pregnancy test within 72 hours prior to lymphodepleting therapy for female participants of childbearing potential. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject is not lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study)
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject does not have rapidly progressive disease, per treating oncologist’s discretion
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION: Subject is a good candidate for CAR.B7-H3 T cell therapy, per treating oncologist’s discretion
• ELIGIBILITY CRITERIA PRIOR TO CELLULAR PRODUCT ADMINISTRATION AFTER LYMPHODEPLETION: Subject has no evidence of uncontrolled infection or sepsis
• ELIGIBILITY CRITERIA PRIOR TO CELLULAR PRODUCT ADMINISTRATION AFTER LYMPHODEPLETION: Negative serum pregnancy within 7 days of the initial cellular product administration. If the pre-lymphodepletion pregnancy test is within the 7 day window, then the pregnancy test does not need to be repeated
• ELIGIBILITY CRITERIA PRIOR TO CELLULAR PRODUCT ADMINISTRATION AFTER LYMPHODEPLETION: Total bilirubin =< 2 x ULN, unless attributed to Gilbert’s syndrome
• ELIGIBILITY CRITERIA PRIOR TO CELLULAR PRODUCT ADMINISTRATION AFTER LYMPHODEPLETION: AST / ALT =< 5 x ULN, unless attributed to intrahepatic liver metastases
• ELIGIBILITY CRITERIA PRIOR TO CELLULAR PRODUCT ADMINISTRATION AFTER LYMPHODEPLETION: Creatinine =< 3 x ULN
• ELIGIBILITY CRITERIA PRIOR TO CELLULAR PRODUCT ADMINISTRATION AFTER LYMPHODEPLETION: Subject has no clinical indication of rapidly progressing disease in the opinion of the clinical investigator
• ELIGIBILITY CRITERIA PRIOR TO CELLULAR PRODUCT ADMINISTRATION AFTER LYMPHODEPLETION: Subject is a good candidate for treatment with CAR.B7-H3 cell product per the clinical investigator’s discretion