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FINDING CURES TOGETHER<sup>SM</sup>

​​​Pembrolizumab Yielded Durable Responses in Patients With Advanced Merkel Cell Carcinoma

4/19/2016

NEW ORLEANS — Many patients with advanced Merkel cell carcinoma (MCC), an aggressive type of skin cancer, who received the immunotherapeutic pembrolizumab as first-line therapy in a phase II clinical trial had durable responses, and responses were seen in those whose cancers were driven by a virus as well as those whose cancers were induced by exposure to ultraviolet (UV) light, according to research presented here at the AACR Annual Meeting 2016, April 16-20. Paul Nghiem

This study is being simultaneously published in The New England Journal of Medicine.

“In this clinical trial, patients with metastatic Merkel cell carcinoma who received pembrolizumab had an objective response rate of 56 percent, which is similar to chemotherapy outcomes, but the duration of response to pembrolizumab appears to be significantly longer than that for chemotherapy,” said Paul Ngheim, MD, PhD, affiliate investigator of the Clinical Research Division at Fred Hutchinson Cancer Research Center in Seattle and professor of medicine, Division of Dermatology, at the University of Washington School of Medicine.

“While the study is still ongoing, the vast majority of patients [86 percent] who responded to pembrolizumab are still experiencing excellent disease control more than six months after starting therapy.”

MCC is a rare, aggressive type of skin cancer, and Merkel polyomavirus (MCPyV) is the driving factor in about 80 percent of MCC cases, Nghiem explained. About 2,000 new cases of MCC are diagnosed in the United States per year. MCC is 35-fold less common than melanoma, but on average, it is about three times more likely to kill a patient than melanoma. Response to chemotherapy is typically quite brief and half of patients develop progressive disease within three months of initiating treatment, he added.

Nghiem and colleagues enrolled 26 patients with advanced/metastatic MCC who had received no prior systemic therapy in this single-arm, open-label trial. Of them, 17 had MCPyV-positive disease. All patients received 2 mg/kg body weight of pembrolizumab every three weeks and responses were assessed every nine to 12 weeks. At the time of data analysis, patients had received four to 49 weeks of therapy.

The overall response rate was 63 percent in patients with virus-positive MCC and 44 percent in those with virus-negative (UV-induced) MCC. Four patients, three with virus-positive disease, had complete responses (CR), and 10 patients, seven with virus-positive disease, had partial responses (PR).

Adverse events in this trial were similar to other anti-PD-1 trials and were largely managed with steroid treatment and stopping the study drug, Nghiem added. The condition of two patients who developed severe drug-related toxicities improved with corticosteroid treatment and discontinuation of pembrolizumab. “Importantly, both these patients have ongoing antitumor responses many months after discontinuation of pembrolizumab,” he noted.

“We believe that the immune system is likely ‘seeing’ different targets in the virus-positive and virus-negative patients,” Nghiem said. He explained that the virus-positive tumors produce the viral proteins needed for the tumors to grow. These viral proteins may be readily seen by the immune system. In contrast, virus-negative MCC has extremely high numbers of mutations caused by sunlight. These mutations can change the normal cellular proteins so they no longer appear as “self” and the immune system can then see and attack these tumors.

Pembrolizumab acts by removing the “brakes” present on tumor-specific immune cells called T cells, thereby allowing the T cells to kill the cancer cells.

“Currently there are no FDA-approved drugs for the treatment of MCC. We are expanding this trial to recruit additional patients and we hope that these data will contribute to meaningful new therapeutic options becoming available for these patients,” Nghiem said.

“It was initially challenging to partner with pharmaceutical companies because of the rarity of MCC. We are very thankful that the National Cancer Institute (NCI)’s Cancer Therapy Evaluation Program (CTEP), the Cancer Immunotherapy Trials Network (CITN), Merck, and multiple clinical sites came together to carry out this challenging study, which we believe is providing significant hope for MCC patients,” he added.

Nghiem is a consultant for EMD Serono, Inc., and receives funding from Bristol-Myers Squibb to perform biomarker studies in MCC clinical trials.