FDA Approves Bavencio for Merkel Cell Carcinoma

Bavencio (avelumab), a PD-L1-inhibitor, gained approval by the Food and Drug Administration (FDA) for the treatment of adult and pediatric patients over the age of 12 with metastatic Merkel cell carcinoma, including those who have never had chemotherapy.

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

“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,” Richard Pazdur, M.D., 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 said in a statement. “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 non-existent.”

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 Bavencio at 10 mg/kg every two weeks. Patients had received at least one prior therapy (59.1 percent), with 11.4 percent having at least three prior system treatments. Most patients in the study were male (73.9 percent) and the ECOG performance status was 0 (55.7 percent) and 1 (44.3 percent).

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

Median progression-free survival (PFS) with Bavencio was 2.7 months. The six-month PFS rate was 40 percent. The median overall survival (OS) was 11.3 months and the six-month OS rate was 69 percent.

In addition to responses, 10.2 percent of patients had stable disease and 20.5 percent were not evaluable for response. Ninety-two percent of patients responded for six or more months and the durable response rate was 29.1 percent.

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

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

Grade 3 AEs were experienced by 4.5 percent 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 Bavencio. Two patients discontinued treatment due to AEs.

The accelerated approval of Bavencio in this setting is contingent upon the results of confirmatory trials.