The primary objective of this pilot study is to assess the feasibility of mobilizing programmed cell death (PD-1)+ T cells to the peripheral blood after a single treatment with tremelimumab/durvalumab in patients with treatment naïve metastatic melanoma.~Secondary objectives are to evaluate the safety and clinical activity of administering a regimen of PD-1+ selected tumor infiltrating lymphocytes (TIL)/(Interleukin) IL-2, using a cell product manufactured in the Yale Advanced Cell Therapy Laboratories and assess for clinical activities in subjects with metastatic melanoma who are not responding or have progressed after receiving first-line therapy with 1 cycle of tremelimumab/durvalumab followed by 3 cycles of ipilimumab/nivolumab followed by nivolumab monotherapy as maintenance treatment.~Exploratory objective are to:~assess the number of PD-1+ T cells in the tumor microenvironment before and after a single treatment with tremelimumab/durvalumab.~conduct a preliminary assessment of the TCR clonotypes present in PD1+ cluster of differentiation 8 (CD8)+ cells (4-1BB, LAG-3, TIM-3, PD-1) versus PD1-CD8+ T-cells early in the expansion cultures and compare to clonotypes late in the final product and in peripheral blood lymphocytes (PBL) 1 and 2 months post infusion.~assess neoantigens present in resected tumor and correlate T cell specificity for neoantigens from TIL and peripheral blood mononuclear cell (PBMC) populations stratified by PD-1 expression in these cell populations.
The primary objective of this pilot study is to assess the feasibility of mobilizing PD-1+ T cells to the peripheral blood after a single treatment with tremelimumab/durvalumab in patients with treatment naïve metastatic melanoma.