The U.S. Food and Drug Administration has approved a novel therapy for patients with metastatic or inoperable melanoma, an aggressive type of skin cancer. The treatment, developed based on original research conducted at the Johns Hopkins Kimmel Cancer Center, is comprised of two immunotherapy agents, relatlimab and nivolumab, which delayed time to cancer progression significantly more than nivolumab alone in a global, multi-center clinical trial.
"The FDA's approval of this novel combination therapy is an exciting development for all of us in the melanoma community," says Evan J. Lipson, an associate professor of oncology at the Johns Hopkins Kimmel Cancer Center and Bloomberg~Kimmel Institute for Cancer Immunotherapy who is a co-author of the study.
Nivolumab acts on a protein called PD-1 and is FDA-approved for treating melanoma and several other cancer types. Relatlimab blocks signaling of an inhibitory protein called LAG-3 displayed on immune system T cells, reinvigorating their anti-tumor activity. Checkpoint inhibitor immunotherapy works by blocking specific proteins on the surfaces of cells that help cancer evade the body's immune system. Blocking these checkpoints helps the immune system fight and eliminate cancer.
In the trial, which was published in The New England Journal of Medicine in January, 714 patients with advanced, previously untreated melanoma were randomized to receive either relatlimab (anti-LAG-3) and nivolumab (anti-PD-1), or nivolumab alone. Median progression-free survival—the length of time that cancer does not worsen—was 10.2 months among patients who received the combination treatment, significantly longer than the 4.6 months seen among those who received nivolumab alone. At one year, progression-free survival was 48% for patients receiving combination therapy and 37% for those receiving nivolumab alone.
"Our collaborative research with scientists and physicians worldwide has demonstrated that targeting LAG-3 effectively activates the immune system against cancer and has established the LAG-3 pathway as the third immune checkpoint pathway in history, after CTLA-4 and PD-1, for which blockade has a clinical benefit," Lipson said.
The anti-tumor effects of LAG-3 blockade were originally co-discovered by scientists at the Bloomberg~Kimmel Institute. Preclinical studies of the combination therapy in mice started at Johns Hopkins in 2010, with a grant from the Melanoma Research Alliance to Johns Hopkins investigators Suzanne L. Topalian, professor of surgery and oncology at Johns Hopkins, and Drew M. Pardoll, director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy and co-director of the Cancer Immunology Program at the Johns Hopkins Kimmel Cancer Center.