FDA Grants Accelerated Approval to Avelumab

First FDA-approved product for treatment of metastatic Merkel cell carcinoma

On 23 March, 2017, the US Food and Drug Administration (FDA) granted accelerated approval to avelumab (Bavencio, EMD Serono, Inc.) for the treatment of patients 12 years and older with metastatic Merkel cell carcinoma. Avelumab is a programmed death-ligand 1 (PD-L1) blocking human IgG1 lambda monoclonal antibody. This is the first FDA-approved product to treat this type of cancer.

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

The ORR was assessed by an independent review committee according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The ORR 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 plus months with 86% of responses durable for 6 months or longer. Responses were observed in patients regardless of PD-L1 tumour expression or presence of Merkel cell polyomavirus.

Safety data were evaluated in 1738 patients who received avelumab, 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, diarrhoea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral oedema. Serious adverse reactions that occurred in more than one patient in the trial were acute kidney injury, anaemia, abdominal pain, ileus, asthenia, and cellulitis. 

The recommended dose and 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. 

Full prescribing information for avelumab is available here.  

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. The approval was granted approximately two months ahead of the goal date.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.