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FDA Grants Priority Review to Avelumab for Merkel Cell Carcinoma

Silas Inman @silasinman
Published: Tuesday, Nov 29, 2016

Dr Luciano Rossetti

Luciano Rossetti, MD

The FDA has granted a priority review to a biologics license application (BLA) for avelumab as a treatment for patients with metastatic Merkel cell carcinoma (MCC), according to a statement from Merck KGaA and Pfizer, the codevelopers of the PD-L1 inhibitor.

The priority review is based on data from the phase II JAVELIN Merkel 200 study, which was presented at the 2016 ASCO Annual Meeting and published in the Lancet Oncology.1,2 In the open-label trial, the objective response rate (ORR) with avelumab was 31.8%, which included a 9.1% complete response rate. After a median follow-up of 10.4 months, 82% of patients continued to respond to therapy.

Under the priority review program, the FDA will decide on the BLA for avelumab within 6 months compared with the standard 10-month review. The accelerated review timeline follows a breakthrough therapy designation for avelumab in MCC that was granted by the FDA in November 2015. The immunotherapy has also received an orphan drug designation and fast track designation for its potential as a treatment for MCC.

“We are pleased the FDA has granted a priority review designation for avelumab,” Luciano Rossetti, MD, executive vice president, Global Head of Research & Development at the biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono, said in a statement. “There are currently no approved treatment options for metastatic MCC, and we are committed to working with the FDA to potentially bring the first approved cancer immunotherapy to patients with this aggressive disease.”

The JAVELIN Merkel 200 study enrolled 88 previously treated patients with metastatic MCC. The median age of patients was 72.5 years, and each received avelumab at 10 mg/kg every 2 weeks. Patients had received at least one prior therapy (59.1%), with 11.4% having ≥3 prior system treatments. Most patients in the study were male (73.9%) and the ECOG performance status was 0 (55.7%) and 1 (44.3%).

The most common site of primary tumor was the skin (76.1%) and all patients had metastatic involvement at the time of study entry. Visceral disease was present for 53.4% of patients. Overall, 65.9% of patients were PD-L1-positive and 52.3% were positive for the Merkel cell polyomavirus (MCPyV). Eight percent of patients were negative for both PD-L1 and MCPyV and 40.9% were positive for both markers.

Median progression-free survival (PFS) with avelumab was 2.7 months (95% CI, 1.4-6.9). The 6-month PFS rate was 40%. The median overall survival (OS) was 11.3 months (95% CI, 7.5-14.0) and the 6-month OS rate was 69%.

In addition to responses, 10.2% of patients had stable disease and 20.5% were not evaluable for response. Ninety-two percent of patients responded for ≥6 months (95% CI, 70-98) and the durable response rate was 29.1%.

The ORR was 34.5% in the PD-L1-positive arm and 18.8% in the PD-L1-negative group. The response rate in those who were not evaluable for PD-L1 status was 35.7%. The ORRs were 26.1% and 35.5% in the MCPyV-positive and -negative arms, respectively. In those not evaluable for the virus the ORR was 45.5%. Patients who were positive for both markers had an ORR of 30.6% and those negative for both markers had an ORR of 28.6%.

Treatment-related adverse events (AEs) of any grade were experienced by 70.5% of patients in the study. The most common AEs, which were mostly grade 1/2, were fatigue (23.9%), infusion-related reaction (17%), diarrhea (9.1%), nausea (9.1%), asthenia (8%), rash (6.8%), decreased appetite (5.7%), and maculopapular rash (5.7%).

Grade 3 AEs were experienced by 4.5% of patients and were mostly laboratory abnormalities, such as lymphopenia, blood CPK increase, transaminase increase, and blood cholesterol increase. There were no grade 4 AEs or deaths related to avelumab. Two patients discontinued treatment due to AEs.

“Metastatic Merkel cell carcinoma is an aggressive disease, and patients face a very poor prognosis, with less than 20% surviving beyond 5 years,” Chris Boshoff, MD, PhD, senior vice president and Head of Immuno-oncology, Early Development and Translational Oncology, Pfizer Global Product Development, said in a statement. “We are encouraged by the results of our phase II trial and believe avelumab may have potential to be an important treatment option for patients living with this hard-to-treat skin cancer.”

An application for avelumab in Merkel cell carcinoma was also been submitted to the European Medicines Agency, in late October 2016. This application was also based on the JAVELIN Merkel 200 study. In addition to MCC, avelumab is also being explored across a variety of other types of cancer that have shown susceptibility to PD-L1 inhibition.
  1. Kaufman H, Russell JS, Hamid O, et al. Avelumab (MSB0010718C; anti-PD-L1) in patients with metastatic Merkel cell carcinoma previously treated with chemotherapy: Results of the phase 2 JAVELIN Merkel 200 trial. J Clin Oncol. 2016;34 (suppl; abstr 9508).
  2. Kaufman H, Russell JS, Hamid O, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016;17(10):1374-1385.

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