NIVO-TIL: Combination anti-PD-1 and adoptive T-cell transfer in metastatic melanoma: a proof of concept

Abstract

Abstract Introduction: Metastatic melanoma patients responding to anti-PD-1 therapy showed proliferation of intra tumoral CD8+ T-cells directly correlated with clinical response, making Tumor-infiltrating lymphocytes (TILs) a potential curative treatment with adoptive cell transfer (ACT). The aim of this trial is therefore to evaluate the safety and efficacy of a sequential combination therapy of Nivolumab (PD-1 inhibitor) and TIL adoptive T-cells in patients with metastatic melanoma. Materials and methods: We performed an explorative, prospective, single-center, open-label, non-randomized, uncontrolled phase I/II study. We enrolled 10 patients with advanced melanoma. Treatment regimen was anti-PD-1 neoadjuvant followed by 2 injections of TILs and a second sequence of anti-PD-1. Results and discussion: Among the 4 patients who received the autologous TILs + Nivolumab combination, 3 (75%) showed an objective response (2 PR at the end of the study followed by 2 CR) and 1 CR at the end of the study. Of these 3, one was PR, and 2 were SD after Nivolumab course and before any TIL administration, reinforcing the value of tumor response after TILs injection. These responses were persistent, from 9 months to 3.4 years.