Intraperitoneal FT538 with Enoblituzumab for the Treatment of 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 FT538 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 FT538 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 poly (ADP-Ribose) polymerase (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 FT538 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 [28 days for pulmonary and cardiac] of study treatment [cyclophosphamide/fludarabine (CY/Flu) or enoblituzumab] start).
• Absolute neutrophil count (ANC) >= 1000 x 10^9/L, unsupported by Granulocyte Colony Stimulating Factor (G-CSF) or granulocytes (within 14 days [28 days for pulmonary and cardiac] of study treatment [CY/Flu or enoblituzumab] start).
• Estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73m2 per current institutional calculation formula (within 14 days [28 days for pulmonary and cardiac] of study treatment [CY/Flu or enoblituzumab] start).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x upper limit of institutional normal (within 14 days [28 days for pulmonary and cardiac] of study treatment [CY/Flu or enoblituzumab] 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 14 days [28 days for pulmonary and cardiac] of study treatment [CY/Flu or enoblituzumab] start).
• Left ventricular ejection fraction (LVEF) >= 40% by echocardiography, MUGA, or cardiac MRI (within 14 days [28 days for pulmonary and cardiac] of study treatment [CY/Flu or enoblituzumab] start).
• 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.
• Agrees to the placement of an intraperitoneal catheter before the 1st dose of study directed drug (chemotherapy or enoblituzumab for Cohort 5 and 6) and remains in place through Day 36 or longer if retreatment is planned.
• 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 be 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 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 CRITERIA: 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 CRITERIA: A functioning IP catheter.
• RETREATMENT CRITERIA: 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 FT538).
• RETREATMENT CRITERIA: All acute treatment related adverse events have resolved to =< Grade 1 or baseline, whichever is higher.
• RETREATMENT CRITERIA: No decline in GOG performance status from baseline as recorded at the Day 36 visit assessment.
• RETREATMENT CRITERIA: Continues to meet laboratory requirements.
• RETREATMENT CRITERIA: If receiving enoblituzumab, able to align retreatment to the third enoblituzumab infusion (receive lymphodepleting chemotherapy within the week after enoblituzumab infusion).
• RETREATMENT CRITERIA: Voluntary written consent using the retreatment consent (CPRC#2021LS103R) 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 or, enoblituzumab, if applicable. 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, at least 4 months after the final dose of FT538, or at least 3 months after the final dose of enoblituzumab, 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 FT538 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 RT), within 2 weeks prior to the first dose of FT538 (or enoblituzumab for Dose Cohorts 5 and 6) or five half-lives, whichever is shorter; or any investigational agent within 28 days prior to the first dose of FT538 (or enoblituzumab for Dose Cohorts 5 and 6).
• Live vaccine within 6 weeks prior to start of lympho-conditioning.
• Known allergy to the following FT538 components: albumin (human) or dimethyl sulfoxide (DMSO).
• Prior enoblituzumab.
• 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 human immunodeficiency virus (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.