Keytruda: New Immunotherapy Drug for Melanoma Wins FDA Approval

The Food and Drug Administration has approved a new type of  immunotherapy drug that will provide a much-needed option for patients with advanced or inoperable melanoma who no longer respond to other drugs – including the immunotherapy agent ipilimumab (Yervoy).

F. Stephen Hodi, MD, director of the Center for Melanoma Oncology at Dana-Farber Cancer Institute
F. Stephen Hodi, MD, director of the Center for Melanoma Oncology at Dana-Farber Cancer Institute

The drug, pembrolizumab or MK-3745, will be marketed under the name  Keytruda. Based on impressive performance in clinical trials, the FDA had designated pembrolizumab a “breakthrough therapy” and placed it on a fast-tracked approval process.

“This drug is exciting because of its really striking response rate and good indications that these responses are durable” for a least a year, says Patrick Ott, MD, PhD, clinical director of the Center for Immuno-Oncology at Dana-Farber.  “And it is very well tolerated, with very manageable side effects,” he adds. The drug has been available, alone and in combination with other drugs, in clinical trials conducted at the center.

Both Keytruda and Yervoy unleash the search-and-destroy power of the body’s immune system against cancer cells. These drugs, as well as others in clinical trials, are arriving on the crest of a new wave of immunotherapy research, in which Dana-Farber scientists have played a prominent role.

Advanced melanoma is responsible for about 9,700 deaths a year in the United States, but the outlook for these patients is growing brighter with the remarkable outcomes brought about by immunotherapy.

The approval of Keytruda marks a first in the United States for a new class of immunotherapy drugs that block the PD-1 protein, which is commandeered by melanoma and other cancer cells to avoid detection and attack by the body’s immune system.

PD-1, along with a pair of partner molecules, PD-L1 (which was discovered by Dana-Farber’s Gordon Freeman, PhD and colleagues) and PD-L2, work together to protect normal cells from being mistakenly harmed by immune soldier cells that defend the body against foreign microbial invaders. Many cancers exploit the PD-1 pathway to hide from the immune response, and drugs like Keytruda inhibit PD-1, stripping the cancer cells of their shield against immune attack.

Keytruda is intended to be used following treatment with ipilimumab, which does not block PD-1 but instead targets another immune-suppressing protein, CTLA-4.

Stephen Hodi, MD, director of the Center for Melanoma Oncology and of the Center for Immuno-Oncology, called the new availability of pembrolizumab  “an important step forward that meets an unmet need” – that is, patients that don’t respond to ipilimumab or other treatments for advanced melanoma.

In an unusually large phase 1 trial of patients whose melanoma had spread throughout the body, Keytruda shrank tumors in about 30 percent of patients – including patients who had failed to respond to ipilimumab. After one year, 69 percent of patients were alive – a sharp improvement over the current outlook for such patients.

Ed. note: The FDA aapproved Bristol-Myers Squibb’s Opdivo, an immunotherapy drug for advanced skin cancer, on Dec. 22, 2014. Like Keytruda, Opdivo blocks the PD-1 protein, which is used by melanoma and other cancer cells to avoid detection and attack from the immune system.