Toripalimab for the treatment of melanoma

ABSTRACT

Introduction

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.

Areas covered

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

Expert opinion

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.

KEYWORDS:

• Adjuvant
• anti-PD-1 antibody
• immunotherapy
• melanoma
• metastatic
• neoadjuvant
• toripalimab

Article Highlights

• Toripalimab and other similar anti-PD-1 antibody products have equivalent efficacy.

• Anti-PD-1 antibody monotherapy is not as effective in treating the types of melanoma most common in Asia (acral and mucosal) as it is in treating non-acral cutaneous melanoma.

• Clinical studies of toripalimab in the neoadjuvant treatment of mucosal melanoma and acral melanoma are ongoing.

• Combination therapy with toripalimab and axitinib, an anti-angiogenic small-molecule targeting drug, represents a novel mode of treatment for melanoma.

• Translational research on combined treatment with toripalimab and other drugs, such as CDK4 inhibitors and CAF inhibitors, may be helpful in overcoming the primary or secondary drug resistance of tumors treated with anti-PD-1 antibody.

This box summarizes key points contained in the article.

Acknowledgments

We thank Dr. Xue Bai and Editors at Medjaden Bioscience Limited for editing the manuscript. And we thank Ph.D. Jinghua Yan, Ph.D. Hui Feng, and Ph.D. Shuguang Tan for providing the graph.

Declaration of interest

J Guo is the member of the advisory board/consultant of MSD, Roche, Pfizer, Bayer, Novartis, Simcere, Shanghai Junshi Bioscience, Oriengene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This study is supported National Natural Science Foundation of China (81672696, 81772912), Beijing Municipal Administration of Hospitals Clinical medicine Development of special funding support (ZYLX201603), and Beijing Municipal Science & Technology Commission (Z161100000516062). Beijing Municipal Administration of Hospitals' Ascent Plan (DFL20181101).