Toripalimab for the treatment of melanoma

Immune therapies have dramatically changed the treatment landscape for melanoma in the past decade. Ipilimumab, nivolumab, and pembrolizumab have been approved by U.S. Food and Drug Administration for the treatment of metastatic melanoma sequentially. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death protein-1 (PD-1), was approved by National Medical Product Administration in China in 2018 as second-line therapy for metastatic melanoma.

This is a comprehensive review of the literature and studies of toripalimab in melanoma, including clinical trials and translational research.

Toripalimab is not inferior to pembrolizumab as a second-line therapy for metastatic melanoma. Prospective validated predictive markers are lacking. Programmed cell death ligand 1 expression and tumor mutational burden are two common recognized biomarkers, but the predictability of these markers requires additional improvement. A number of studies have confirmed that PD-1 inhibitors, including toripalimab, are not as effective in mucosal and acral melanomas as in non-acral cutaneous subtype. Toripalimab in combination with tyrosine kinase inhibitor axitinib has shown a promising result for metastatic mucosal melanoma. It is crucial to explore the mechanisms underlying the varying biological behavior of melanoma subtypes, which may also provide clues of innate and acquired resistance to PD-1 blockade.