Lambrolizumab shows significant antitumor activity in patients with advanced melanoma

Researchers from UCLA's Jonsson Comprehensive Cancer Center led by Dr. Antoni Ribas, professor of medicine in the division of hematology-oncology, report preliminary results showing significant antitumor activity with very manageable side effects from a new drug being tested in patients with advanced melanoma, the deadliest form of skin cancer.

Ribas presented the results at the 2013 meeting of the American Society of Clinical Oncology this morning in Chicago, and the study was published online ahead of press in The New England Journal of Medicine immediately afterward. The drug, lambrolizumab (also known as MK3475), discovered and developed by Merck, received "Breakthrough Therapy" designation from the United States Food and Drug Administration (FDA) in April.

Results
These results are from the first clinical trial of lambrolizumab in patients with advanced melanoma and are based on analysis of 135 patients with metastatic melanoma who were divided into three groups with different treatment regimens.

Overall, lambrolizumab resulted in 38% of patients having confirmed improvement of their cancer across all dose levels given. This ranged between 25% in patients who received the lowest dose, to 52% in patients who received the highest dose. The rate of any tumor response across all patients was 77%. The average duration of response to the drug has not been reached because only five patients who had initial responses have been taken off the study because their cancers got worse. At this point the longest response has been over 1 year.

Side effects with lambrolizumab are usually mild and easily managed. These include fatigue, fevers, skin rash, loss of skin color and muscle weakness. Only 13% of patients had side effects that were of higher severity, including inflammation of the lung or kidney, and thyroid problems.

According to Ribas, "this study is showing the highest rate of durable melanoma responses of any drug we have tested thus far in this cancer, and it is doing it without serious side effects in the great majority of patients."

Drug Mechanism
T cells are the human immune system's soldiers that find and destroy invaders that cause infections and diseases in the body. Cancers like melanoma are usually not detected by the immune system, and they spread without T cells destroying them. One problem may be that a protein called PD-L1 on the surface of cancer cells allows them to hide from T cells that express the protein PD-1 on their surfaces. Lambrolizumab is an antibody that blocks PD-1 and reactivates an immune response to the cancer cells.

"Lambrolizumab turns on the body's immune system to attack the cancer, and the immune system seems to remember that the melanoma is the enemy and continues to control it long term," Ribas states.

These data have led to a series of additional studies testing lambrolizumab in patients with melanoma and other cancers, including lung cancer.