Infusion of Autologous T Cells Engineered to Target FSH Receptor in Recurrent Ovarian Cancer

Inclusion Criteria:

• Aged 18 years or older and able to provide informed consent.

• Pathologically confirmed diagnosis of invasive (Grades 1-3) epithelial ovariancancer, primary peritoneal cancer, or fallopian tube carcinoma (EOC), which areserous, endometrioid, clear cell, mucinous, mixed epithelial, or undifferentiated.Borderline serous ovarian tumors (BOT, also known as serous low-malignant potentialtumors) are included, as are mixed invasive/borderline cancers. Patients may alsohave sex cord-stromal tumors (SCSTs) to include adult-type granulosa cell tumors (GCTs) and Sertoli Leydig cell tumors (SLCTs), or SCSTs with mixed elements thatinclude at least one of these types.

• Have measurable disease or detectable (non-measurable) disease.

• Consent to have tumor obtained for correlative study testing.

• Patients must have had 1 prior platinum-based chemotherapeutic regimen for themanagement of ovarian, primary peritoneal, or fallopian tube carcinoma and at least 2 prior chemotherapy regimens.

• Patients should be considered platinum- refractory (progression while on a priorplatinum chemotherapy) or resistant (persistence or recurrence within 6 months aftera prior platinum chemotherapy) and be deemed unlikely to have significant benefitfrom any standard therapies by the treating investigator.

• Patients with a known germline or somatic BRCA pathogenic mutation should receive aPARP inhibitor if treatment would be consistent with the current FDA approval foruse of PARPi at time of screening, unless they have a documented history ofintolerance or inability to swallow oral medications.

• For Granulosa Cell Tumors (GCTs), at least one hormonal regimen (i.e., letrozole)should be included in prior therapies.

• For Borderline Ovarian Tumors, documentation of the consideration of a MEK inhibitor (e.g., trametinib) should be included.

• For high-grade serous (Grades 2,3), eligibility and consideration of FolateReceptor-alpha antibody drug conjugate (e.g., mirvetuxumab) should be considered anddocumented for patients who meet all FDA label criteria.

• Patients are allowed to receive, but are not required to receive, up to 6 additionalprior (for a total of 8 prior treatments) chemotherapy treatment regimens (includingplatinum-based chemotherapy). Prior maintenance therapy with an agent when there hasnot been progression will not be a separate treatment regimen. Prior hormonaltherapy is allowed, and when used alone, even as a therapeutic agent, it does notcount toward this prior regimen requirement. Hormonal therapy must be discontinuedat least 1 week before T-cell infusion. Continuation of hormone replacement therapyis permitted.

• Patients are allowed to receive, but are not required to receive, biologic/targetedtherapy alone or as part of their treatment regimens. When used as treatment afterprogression, these treatments will count as a separate therapy.

• Eastern Cooperative Oncology Group (ECOG) status of 2 or better (or KarnofskyPerformance Status score of ≥60%).

• Life expectancy of at least 3 months.

• Adequate bone marrow, renal, and hepatic function (liver function and renal tests,grade 1 or lower):

• No anticancer therapy (chemotherapy, biologic therapy, or immunotherapy) in the 3weeks before the T-cell infusion (and all hematologic effects have resolved).

• No prior immunotherapy with checkpoint blockade (e.g., PD1 inhibitor, PDL1inhibitor, or CTL4- antagonist or similar agent) in the 3 months before the T-cellinfusion (and all clinically significant related side effects must be resolved).

• Patient agrees to undergo placement of surgically placed peritoneal port and centralline catheter. (may be temporary or subcutaneous).

• Although it is anticipated that patients who are eligible for this study will nothave childbearing potential, any patient the treating doctor or investigator deemsto have childbearing potential must agree to an acceptable means of contraceptionfrom the time of screening to at least 6 months after T-cell infusion.

Exclusion Criteria:

• Known active hepatitis B infection, known history of hepatitis C or HIV infection.

• Clinical or radiographic evidence of bowel obstruction or need for parenteralhydration and/or nutrition.

• Known or suspected extensive abdominal adhesions that would preclude port placementor infusion.

• Any of the following cardiac conditions:

Clinically significant heart disease (New York Heart Association class 3 or 4) or symptomatic congestive heart failure.

Myocardial infarction <6 months before enrollment. History of clinically significant ventricular arrhythmia or unexplained syncope that is not believed to be vasovagal in nature or due to dehydration.

History of severe non-ischemic cardiomyopathy with ejection fraction <20%. Findings on baseline ECG or ECHO that, in the opinion of the patient's treating physician or investigator, would require medical intervention before anticancer therapy

• Active autoimmune disease (excluding autoimmune thyroid disease on a stable thyroidregimen). Such conditions include but are not limited to systemic lupuserythematous, rheumatoid arthritis, ulcerative colitis, Crohn's disease, andtemporal arteritis.

• Known or suspected leptomeningeal disease and patients with metastases to the brainstem, midbrain, pons, or medulla.

• Known or suspected untreated brain metastases. Patients with radiographicallystable, asymptomatic previously irradiated lesions are eligible provided patient is >4 weeks beyond completion of cranial irradiation and >3 weeks off of corticosteroidtherapy at the time of study intervention.

• Prior history of clinically significant seizure disorder (e.g., not includingchildhood febrile seizures).

• Any concurrent active malignancies, defined as malignancies requiring any therapyother than expectant observation, because adverse events (AEs) resulting from thesemalignancies or their treatment may confound our assessment of the safety ofadoptive T-cell therapy for ovarian cancer.

• Prior radiotherapy to any portion of the abdominal cavity or pelvis.

• Current lactation or pregnancy

• Any of the following within 28 days of first date of study treatment:

Serious uncontrolled medical illness or disorder that in the opinion of the treating physician would make the patient ineligible for the study.

Active uncontrolled infection (with the exception of uncomplicated urinary tract infection).

Abdominal fistula, gastrointestinal perforation, or intraabdominal abscess. Abdominal surgery (for reasons other than IP port placement).

• Any other issue which, in the opinion of the treating physician or principalinvestigator, would make the patient ineligible for the study.