Researchers report that investigative lambrolizumab has shown promising results, in advanced melanoma, with manageable side effects.
The findings were presented at ASCO on June 2, 2013 by lead investigator Antoni Ribas, MD, professor of medicine in the UCLA division of hematology-oncology, Jonsson Comprehensive Cancer Center in Los Angeles. The study was published simultaneously online in the New England Journal of Medicine.
“This study is showing the highest rate of durable melanoma responses of any drug we have tested thus far for melanoma, and it is doing it without serious side effects in the great majority of patients,” Ribas said.
This is the first clinical trial (Phase I) of investigative lambrolizumab (MK3475).
As background, the authors noted that T cells find and destroy invaders that cause infections and diseases, and cancers like melanoma are usually undetected by the immune system, spreading without T cells activation. A protein called PD-L1 on the surface of cancer cells disguises them from from T cells. Lambrolizumab 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 said.
The researchers enrolled 135 subjects with advanced metastatic melanoma, who were divided into three different treatment dosing groups.
Dr. Ribas reported that 38 percent of all subjects treated with lambrolizumab saw confirmed improvement of their cancer, across all dose levels.
Of subjects taking the lowest dose, 25 percent showed improvement. And 52 percent of subjects taking the highest dose improved.
Rate of any tumor response for all subjects was 77 percent.
Researchers have not enumerated average duration of response to the drug, since only 5 subjects with initial response were taken out of the study when their cancers worsened. The longest response to date is over 1 year.
Side effects included fatigue, fever, skin rash, loss of skin color and muscle weakness. Thirteen percent of patients had side effects that were more severe, including inflammation of the lung or kidney, and thyroid problems.
Additional studies of lambrolizumab in patients with melanoma and other cancers, including lung cancer, are underway.
Lambrolizumab received “breakthrough therapy” designation from the U.S. Food and Drug Administration in April of 2013. Part of the 2012 FDA Safety and Innovation Act, the “breakthrough therapy” designation expedites development and review of a potential new medicine if it is “intended, alone or in combination with one or more other drugs, to treat a serious of life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.”
This research was supported by Merck Sharp & Dohme Corp.