Avelumab Recommended for EU Approval for Merkel Cell Carcinoma

Chris Boshoff, MD, PhD

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended approval of avelumab (Bavencio) for adults with metastatic Merkel cell carcinoma, according to Pfizer and Merck, the codevelopers of the PD-L1 inhibitor.

The European Commission is expected to rule on the application later this year. If approved, avelumab would be the first immunotherapy treatment indicated for metastatic Merkel cell carcinoma in the European Union.

“Metastatic Merkel cell carcinoma is a devastating disease and patients in Europe currently have very few treatment options,” Chris Boshoff, MD, PhD, senior vice president and head of Immuno-Oncology, Early Development, Translational Oncology, Pfizer Global Product Development said in a press release. “This milestone further demonstrates our commitment to tackle hard-to-treat cancers as we continue to explore the potential of avelumab in other tumors.”

The CHMP’s opinion was based on data from the phase II JAVELIN Merkel 200 study. In the open-label trial, the objective response rate (ORR) with avelumab was 33% (95% CI, 23.3-43.8), which included an 11.4% (95% CI, 6.6-19.9) complete response rate and a 21.6% (95% CI, 13.5-31.7) partial response rate. The duration of response (DOR) was at least 6 months in 86% of patients, with 45% of patients having a DOR of 12 months or more.

Results from the JAVELIN Merkel 200 study, which enrolled 88 previously treated patients with metastatic Merkel cell carcinoma, were previously presented at the 2016 ASCO Annual Meeting and published in the Lancet Oncology.1,2 The median age of patients in the study was 72.5 years, and each received avelumab at 10 mg/kg every 2 weeks. Patients had received at least 1 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%.

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.

The FDA granted an accelerated approval to avelumab in May 2017, making it the first treatment approved by the FDA for metastatic Merkel cell carcinoma. The accelerated approval of avelumab in this setting is contingent upon the results of confirmatory trials.

References

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.