Lifileucel With Reduced Dose Fludarabine/Cyclophosphamide Lymphodepletion and Interleukin-2 for the Treatment of Patients With Unresectable or Metastatic Melanoma

PRIMARY OBJECTIVE: I. The percentage of total TIL clones as measured by the T-cell receptor (TCR) population shared between the tumor infiltrating lymphocyte (TIL) product and peripheral blood mononuclear cells (PBMC). SECONDARY OBJECTIVES: I. To evaluate the efficacy parameters of lifileucel (LN-144) in combination with a reduced dose lymphodepletion in patients with unresectable or metastatic melanoma by assessing objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). II. To characterize the safety profile of lifileucel (LN-144) in combination with a reduced dose lymphodepletion regimen in patients with unresectable or metastatic melanoma. EXPLORATORY OBJECTIVE: I. Blood and tumor samples will be banked for future correlative analyses, including flow cytometry, next generation sequencing, immunogenomics and RNA sequencing to characterize the immunome and microenvironment. OUTLINE: Patients undergo tumor resection surgery. After the lifileucel is manufactured (approximately 4 weeks later), patients receive cyclophosphamide intravenously (IV) on days -4 to -2 and fludarabine IV on days -4 to -1. Patients then receive lifileucel IV on day 0. Patients also receive up to 6 doses of intraleukin-2 IV. After completion of study treatment, patients are followed up at day 28, 42, 84, 126, 180, 365, month 18, and month 24.