AVELUMUMAB APPROVED FOR MERKEL CELL CARCINOMA

The U.S. Food and Drug Administration (FDA) today granted accelerated approval to avelumab (Bavencio) for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma, including those who have not received prior chemotherapy. Avelumab is a programmed cell death ligand 1 (PD-L1)–blocking human IgG1 lambda monoclonal antibody. This is the first FDA-approved treatment for metastatic Merkel cell carcinoma, a rare, aggressive form of skin cancer.

Avelumab received Orphan Drug status and Breakthrough Therapy designation for this indication, and the application was granted priority review. As a condition of accelerated approval, an additional study is required to confirm the clinical benefit of avelumab for this indication.

“While skin cancer is one of the most common cancers, patients with a rare form called Merkel cell cancer have not had an approved treatment option until now,” said Richard Pazdur, MD, Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and Director of the FDA’s Oncology Center of Excellence. “The scientific community continues to make advances targeting the body’s immune system mechanisms for the treatment of various types of cancer. These advancements are leading to new therapies—even in rare forms of cancer where treatment options are limited or nonexistent.”

According to the National Cancer Institute, approximately 1,600 people in the United States are diagnosed with Merkel cell carcinoma every year. Although the majority of patients present with localized tumors that can be treated with surgical resection, approximately half of all patients will experience recurrence, and more than 30% will eventually develop metastatic disease.

JAVELIN Merkel 200 Trial

Approval was based on data from the JAVELIN Merkel 200 trial, an open-label, single-arm, multicenter clinical trial demonstrating a clinically meaningful and durable overall response rate. All patients had histologically confirmed metastatic Merkel cell carcinoma with disease progression on or after chemotherapy administered for metastatic disease. 

Overall response rate was assessed by an independent review committee according to Response Evaluation Criteria in Solid Tumors 1.1. The overall response rate was 33% (95% confidence interval [CI] = 23.3%–43.8%), with 11% complete and 22% partial response rates. Among the 29 responding patients, the response duration ranged from 2.8 to 23.3+ months, with 86% of responses durable for 6 months or longer. Responses were observed in patients regardless of PD-L1 tumor expression or presence of Merkel cell polyomavirus.

Safety Data

Safety data were evaluated in 1,738 patients who received avelumab at 10 mg/kg, every 2 weeks. The most common serious adverse reactions to avelumab are immune-mediated adverse reactions (pneumonitis, colitis, hepatitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus, and nephritis) and life-threatening infusion reactions. Among the 88 patients enrolled in the JAVELIN Merkel 200 trial, the most common adverse reactions were fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral edema. Serious adverse reactions that occurred in more than one patient in the trial were acute kidney injury, anemia, abdominal pain, ileus, asthenia, and cellulitis. 

The recommended dose/schedule of avelumab is 10 mg/kg as an intravenous infusion over 60 minutes every 2 weeks. All patients should receive premedication with an antihistamine and acetaminophen prior to the first four infusions of avelumab.