Nivolumab and pembrolizumab as immune-modulating monoclonal antibodies targeting the PD-1 receptor to treat melanoma

Abstract

Malignant melanoma is an important issue in oncology due to its high incidence, high mortality, and resistance to systemic therapy; however, targeted immunotherapy has noticeably improved the survival rates of melanoma patients. Promising targeted immunotherapies for malignant melanoma include the blockade of immune checkpoints with antibodies targeting cytotoxic T lymphocyte-associated antigen 4 and the programmed cell death protein 1 pathway. The US FDA-approved antibody ipilimumab targets cytotoxic T lymphocyte-associated antigen 4; however, it was limited by toxicity and a low response. Nivolumab and pembrolizumab (formerly lambrolizumab), the two FDA-approved anti-programmed death-1 monoclonal antibodies, show highly durable response rates and long-term safety, validating the importance of the programmed cell death protein 1 pathway blockade for treatment of malignant melanoma.

Keywords:

• melanoma
• monoclonal antibody
• nivolumab
• PD-1 receptor
• pembrolizumab

Financial & competing interests disclosure

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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Nivolumab and pembrolizumab are monoclonal immunoglobulin G4 antibodies that bind selectively to PD-1, blocking its interaction with both ligands in the tumor microenvironment.

• In a Phase I study of nivolumab in patients with a variety of solid tumors, the notable durability of objective responses and low toxicity, suggested potential of the drug to be administrated in an outpatient setting with the least supportive concern.

• In Phase III study in previously untreated metastatic melanoma patients without a BRAF mutation, nivolumab demonstrated higher OS and PFS rate and more acceptable safety profile than DTIC.

• Phase I and II studies of pembrolizumab showed high and durable response rate in patients with progressive melanoma similar to the response pattern of nivolumab.

• Pembrolizumab and nivolumab was approved by US FDA in December and September, respectively, in 2014 for the treatment of advanced and metastatic malignant melanoma.

Notes