A Phase II Trial of Tumour Infiltrating Lymphocyte Adoptive Cell Therapy in Patients With Immune Checkpoint Inhibitor Resistant Unresectable or Metastatic Melanoma

This is a single arm, open label phase II study to determine the activity of Perkileucel, a tumour infiltrating lymphocyte (TIL) adoptive cell transfer therapy (ACT), in patients with unresectable stage III or metastatic melanoma who have progressed on previous treatment with immune checkpoint inhibitors in the adjuvant or metastatic setting. Patients with sufficient and accessible tumour tissue measuring at least 1.5 cm will undergo surgical excision. Harvested tumour tissue will be cultured at CTTWA and TIL will be expanded within 5 weeks. Five days prior to infusion of TIL-ACT, patients will receive a nonmyeloablative lymphodepleting regimen with cyclophosphamide (60 mg/kg) once daily concurrently with fludarabine (25 mg/m\^2) IV once daily for 2 days followed by fludarabine (25mg/m\^2) once daily for 3 days. Patients will then receive a single dose of TIL-ACT of 1 × 10\^9 to 2 × 10\^11 TIL intravenously on Day 0. Patients will receive up to 6 doses of intravenous high-dose interleukin-2 (600 000 IU/kg IV) every 8-12 hours. The total inpatient stay from chemotherapy to recovery after IL-2 will be approximately 15 days. Blood tests and imaging assessments will be performed regularly to monitor safety and response. The total duration of the study is 8 years. Safety will be assessed throughout the full duration of the study. Patients will be monitored for delayed adverse events. The assessment of the activity of TIL ACT in patients unresectable or metastatic melanoma resistant to anti-PD1 will be performed using best objective response rate as per RECIST criteria 1.1.