OVSTAR TIL Trial (OVarian Cancer Co-STimulatory Antigen Receptor TIL Trial)

This is a single-arm Phase 1/2a study of unmodified (UTIL-01) and gene modified (CoTIL-01) adoptive TIL therapy which will enrol sequentially. A total of 8 patients will be recruited to the UTIL-01 cohort to receive autologous standard unmodified TIL (phase 2). Up to 14 patients will receive autologous gene engineered TIL(CoTIL-1) in a dose escalation design (Phase 1/2a). Once patients have met all the pre-screening inclusion criteria, and that sponsor has confirmed a successful TIL harvest, a request to manufacture will be sent to the Sponsor to initiate TIL production. Manufacturing and quality control assessment is anticipated to take approximately 6 weeks. During this time, patients may receive standard of care chemotherapy (bridging chemotherapy) as deemed appropriate by the treating oncology team. Patients will proceed to the main trial after completion of bridging chemotherapy. Once the TIL product is certified for release, and that patient has consented to the main trial and has completed main trial screening assessments, study treatment can be scheduled. Patients will receive non-myeloablative lymphodepleting pre-conditioning chemotherapy with cyclophosphamide 600mg/m2/day and fludarabine 30mg/m2/day on Day -5, -4 and -3. Chemotherapy will aim to be delivered as an outpatient, but patients can be admitted if clinically needed. Patients will be required to maintain oral hydration of \>2 litres per day. If this is felt to be difficult to achieve then the patient will be admitted for IV fluids. Patients will be admitted for TIL infusion on Day 0. The TIL infusion will be administered at least 36 hours after last dose of chemotherapy. The cells will only be thawed once an Investigator has made a positive decision to go ahead with infusion and confirmed this in writing. TIL infusion may be delayed for up to 7 days for clinical reasons or for issues regarding the cell specification. This decision must be made before final preparation for infusion. Following TIL infusion, patients will commence subcutaneous interleukin-2 at a fixed dose of 18 million units once a day. Patients must remain an inpatient for the duration of IL-2 treatment for a minimum of 7 days post TIL infusion. Recruitment to the study will occur over approximately 24-month period. Recruitment to CoTIL-01 will commence after UTIL-01. Patients will be followed up in the study for 24 months post TIL infusion.