Emerging PD-1/PD-L1 antagonists for the treatment of malignant melanoma

ABSTRACT

Introduction

Increased understanding of the interactive mechanisms between tumors and the immune system led to the development of immune checkpoint inhibitors, which have revolutioned the treatment of metastatic melanoma and subsequently many other tumors. In 2014, nivolumab and pembrolizumab, two checkpoint inhibitors binding to PD-1, were approved for the treatment of metastatic melanoma. Since then, a plethora of new molecules have enriched the armamentarium against melanoma.

Areas covered

This review summarizes the last updates about treatment with nivolumab and pembrolizumab, data on other PD-1/PDL-1 agents such as spartalizumab and atezolizumab and emerging compounds, new combinations with NKTR-214, anti LAG-3, anti IDO-1 and TVEC, new checkpoint inhibitors (e.g. TIM-3 or TIGIT) and other new molecules for the treatment of metastatic melanoma.

Expert opinion

Currently, several ongoing clinical trials are investigating novel molecules, or immunotherapy combinations, in order to achieve even better survival outcomes for patients, overcoming resistance mechanisms and improving toxicity profiles. The challenge in the near future will be to select the most appropriate treatments according to the specific characteristics of the patients.

KEYWORDS:

• PD-1
• pd-L1
• spartalizumab
• atezolizumab
• nktr-214
• lag-3
• ido-1
• tvec
• tim-3
• tigit

Declaration of interest

V Vanella and L Festino have disclosed a relationship with MSD and Novartis. PA Ascierto has disclosed a relationship with Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Array, Merck Serono, Pierre-Fabre, Incyte, Medimmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Indera, Ultimovacs, Sandoz, Immunocore,4SC, Alkermes, Italfamaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec. PA Ascierto also received research funding from Bristol Myers Squibb, Roche-Genentech, Array, Sanofi, and travel support from MSD. 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 or other relationships to disclose.

Additional information

Funding

This paper was not funded.