Intraperitoneal FT536 with Lymphodepleting Chemotherapy for the Treatment of Patients with Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Inclusion Criteria

• Recurrent epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer meeting one of the following minimal prior treatment requirements (no limit to the maximum number of prior treatments). * Platinum resistant: may receive FT536 as 2nd line (as 1st salvage therapy). Platinum resistant is defined as disease that has responded to initial chemotherapy but demonstrates recurrence within a relatively short period of time (< 6 months) following the completion of treatment. * Platinum sensitive: may receive FT536 as 3rd line therapy (as 2nd salvage therapy). Platinum sensitive is defined as the recurrence of active disease in a patient who has achieved a documented response to initial platinum based treatment and has been off therapy for an extended period of time (≥ 6 months)
• Must have received prior bevacizumab
• In the presence of a BRCA mutation, must have received a prior PARP inhibitor
• Measurable disease per Response Evaluation Criteria in Solid Tumors version (v) 1.1 (RECIST) within the abdomen and pelvis assessed within 42 days of the 1st FT536 infusion. Extra-peritoneal disease is permitted; however each lesion must be < 5 cm at the largest diameter
• At least 18 years of age at the time of consent
• Gynecologic Oncology Group (GOG) performance status 0, 1, or 2
• Platelets ≥ 75,000 x 10^9/L (within 14 days of study treatment [cytarabine (CY)/fludarabine (Flu]) start unsupported by granulocyte colony stimulating factor [G-CSF] or granulocytes)
• Absolute neutrophil count (ANC) ≥ 1000 x 10^9/L (within 14 days of study treatment [CY/Flu] start unsupported by G-CSF or granulocytes)
• Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m^2 per current institutional calculation formula (within 14 days of study treatment [CY/Flu] start)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of institutional normal (within 14 days of study treatment [CY/Flu] start)
• Oxygen saturation ≥ 90% on room air; pulmonary function tests (PFTs) are performed only if known history or as medically indicated – if done, must have pulmonary function >50% corrected carbon monoxide diffusing capability (DLCO) and forced expiratory volume in 1 second (FEV1) (within 28 days of study treatment [CY/Flu] start)
• Left ventricular ejection fraction (LVEF) ≥ 40% by echocardiography, MUGA, or cardiac MRI; no clinically significant cardiovascular disease including any of the following: stroke or myocardial infarction within 6 months prior to first study treatment; unstable angina or congestive heart failure of New York Heart Association (NYHA) grade 2 or higher (within 28 days of study treatment [CY/Flu] start)
• Agrees to the placement of an intraperitoneal catheter before the 1st dose of study directed drug (chemotherapy) and remains in place through day 36 or longer if retreatment is planned. Refer to protocol document if catheter cannot be successfully placed
• Agrees to undergo a tumor biopsy if feasible at the time the catheter is placed and removed – Accessible tumor for biopsy is not required for eligibility
• If history of brain metastases must be stable for at least 3 months after treatment – A brain CT scan or MRI is only required in patients with known brain metastases at the time of enrollment or in those with clinical signs or symptoms suggestive of brain metastases
• Must agree to and sign the consent for the companion Long-Term Follow-Up study (CPRC# 2021LS077) to fulfill the Food and Drug Administration (FDA) recommended 15 years of follow up for a genetically modified cell product
• Voluntary written consent prior to the performance of any research related procedures
• RETREATMENT: Achieved clinical benefit from the 1st treatment course (stable disease, partial response [PR] or complete response [CR] based on RECIST) when comparing baseline CT scan and the CT scan performed around day 36
• RETREATMENT: A functioning IP catheter
• RETREATMENT: No unacceptable toxicity (experienced toxicity that met the definition of a dose-limiting toxicity [DLT] and/or toxicity that caused a dose to be skipped during the first course of FT536)
• RETREATMNET: All acute treatment related adverse events have resolved to ≤ grade 1 or baseline (except for grade 2 lymphopenia), whichever is higher
• RETREATMENT: No decline in GOG performance status from baseline as recorded at the day 36 visit assessment
• RETREATMENT: Continues to meet laboratory requirements for first treatment
• RETREATMENT: Voluntary written consent using the retreatment consent (CPRC# 2023LS185R) prior to any retreatment activities

Exclusion Criteria

• Pregnant or breastfeeding or planning on becoming pregnant in the next 6 months. If of childbearing potential (have a uterus and ovaries) and engaged in heterosexual intercourse, must have a negative pregnancy test (serum or urine) within 14 days before the 1st CY/Flu. Patient must agree to use highly effective method of birth control from the screening visit until at least 12 months after the final dose of CY, or at least 4 months after the final dose of FT536, whichever is longer
• Currently receiving or likely to require systemic immunosuppressive therapy (e.g., prednisone > 5 mg daily) for any reason from day -5 to 14 days after the last FT536 infusion) with the exception of corticosteroids as a pre-medication per institutional standard of care – topical and inhaled steroids are permitted
• Active autoimmune disease requiring systemic immunosuppressive therapy
• History of severe asthma and currently on chronic systemic medications
• Uncontrolled bacterial, fungal or viral infections with progression of clinical symptoms despite therapy
• Receipt of any biological therapy, chemotherapy, or radiation therapy (except palliative radiation therapy [RT]), within 2 weeks prior to the first dose of FT536 or five half-lives, whichever is shorter; or any investigational agent within 28 days prior to the first dose of FT536
• Live vaccine within 6 weeks prior to start of lympho-conditioning
• Known allergy to the following FT536 components: albumin (human) or dimethyl sulfoxide (DMSO)
• Grade ≥ 2 ascites at the time of enrollment
• Non-malignant central nervous system (CNS) disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment
• Known history of HIV positivity or active hepatitis C or B - chronic asymptomatic viral hepatitis is allowed
• Presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to patient
• Any medical condition or clinical laboratory abnormality that, per investigator judgement, precludes safe participation in and completion of the study or that could affect compliance with protocol conduct or interpretation of results