The Food and Drug Administration has granted accelerated approval to avelumab for the treatment of metastatic Merkel cell carcinoma (MCC) in adult and pediatric patients aged 12 years and older.
Avelumab, a programmed death-ligand 1 (PD-L1)–blocking human IgG1 lambda monoclonal antibody, is the first FDA-approved treatment for metastatic MCC.
Approval was based on a 33% overall response rate in a single arm trial (JAVELIN Merkel 200 trial) of 88 patients with metastatic MCC who had been previously treated with at least one prior chemotherapy regimen, the FDA said in a written statement.
The response duration among that 33% ranged from 2.8 to 23.3+ months, and 86% of responses were durable for 6 months or more. “Responses were observed in patients regardless of PD-L1 tumor expression or presence of Merkel cell polyomavirus,” the FDA said.
There were safety data in 1,738 patients, who received 10 mg/kg of avelumab every 2 weeks. Immune-mediated adverse reactions (pneumonitis, colitis, hepatitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus, and nephritis) and life-threatening infusion reactions were the most common, serious adverse events associated with avelumab. Of the 88 patients 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 FDA said.
The recommended dose of avelumab is 10 mg/kg administered in an intravenous infusion over 60 minutes every 2 weeks. Labeling includes the recommendation that all patients should be premedicated with an antihistamine and acetaminophen before each of the first four infusions.
“As a condition of accelerated approval, an additional study is required to confirm the clinical benefit of avelumab for this indication,” according to the FDA.
The drug is being marketed as Bavencio by EMD Serono.