MSK Plays Critical Role in FDA Approval of New Melanoma Drug

MSK Plays Critical Role in FDA Approval of New Melanoma Drug

On December 22, the US Food and Drug Administration approved a new treatment for people with melanoma that cannot be surgically removed or has metastasized, or spread, and no longer responds to other therapies. After the drug, nivolumab (Opdivo™), was shown to shrink tumors in a clinical trial, it received accelerated approval, which allows patients earlier access to promising therapies that show effectiveness during a study.

Memorial Sloan Kettering physicians helped spearhead clinical trials testing nivolumab’s safety and effectiveness and continue to conduct studies using the drug to treat melanoma and other cancers. In particular, MSK was one of the primary sites for the multi-center phase III trial that directly led to the FDA approval, enrolling a large number of patients in the study.

Nivolumab inhibits the PD-1 protein, a molecule on the surface of immune cells that acts as a brake to prevent the immune system from attacking tumors. Blocking PD-1 takes the brakes off and allows the immune cells to destroy the cancer.

A Striking Result

Metastatic melanoma is the deadliest form of skin cancer, and until recently treatment options had been very limited for those whose cancer progressed after initial treatment. In the phase III trial, nivolumab shrank tumors in 32 percent of patients — an effect that lasted for more than six months in approximately one-third of those who experienced the reduction.

“This type of dramatic benefit is not typically seen in cancer patients. These are patients who did not respond to other standard therapies, so these drugs are really practice-changing,” says medical oncologist Sandra D’Angelo, who led the MSK portion of the trial along with medical oncologist and immunologist Jedd Wolchok.

The FDA approved nivolumab for patients whose melanoma has progressed after previously being treated with ipilimumab (Yervoy™) — another drug that harnesses the immune system — and also for patients whose tumors express a gene mutation called BRAF V600 and who have already received ipilimumab and a BRAF inhibitor.

Dr. Wolchok and MSK medical oncologist Michael Postow are now leading clinical studies testing nivolumab as an initial frontline therapy in melanoma patients.

Immunotherapy: The New Paradigm

Nivolumab is the latest in a new generation of cancer therapies that unleash the immune system to destroy cancer cells. This approach, which MSK physician-scientists played a major role in developing, is producing stunning results when combined with standard anticancer therapies.

The first such immunotherapy drug, ipilimumab, was approved in 2011 and acts on a different immune cell protein called CTLA-4 to achieve a similar effect.  Much of the basic research identifying CTLA-4 as a critical target was done by immunologist James Allison, who spent nearly a decade of his career at MSK before leaving in 2012 for MD Anderson Cancer Center in Houston. Ipilimumab has already produced impressive results in some melanoma patients, dramatically extending life expectancy.

In September 2014, another drug, pembrolizumab (Keytruda™), became the first anti-PD-1 therapy to be approved by the FDA, also for the treatment of advanced melanoma. Dr. Wolchok helped guide both ipilimumab and pembrolizumab through late-stage clinical trials.

“Our approach to melanoma has really been transformed over the last three years, beginning with the approval of ipilimumab,” Dr. D’Angelo says. “Patients are now living with a disease for which there had been no effective options. It’s a testament to our involvement and commitment to immunotherapy and Dr. Wolchok’s ability to make this happen here at our institution.”

The impact of nivolumab and similar immunotherapy drugs extends well beyond melanoma. Dr. D’Angelo says her main interest now lies in using immunotherapy to treat sarcoma, a type of cancer which, like melanoma, also has had limited treatment options. She will be leading a phase II clinical trial opening in the spring of 2015 testing nivolumab alone or in combination with ipilimumab in sarcoma patients. The national study will be conducted through the Alliance for Clinical Trials in Oncology, a network sponsored by the National Cancer Institute.