Regulatory Decision Summary for Bavencio

Authorization was based on an ad hoc analysis from an ongoing single arm study conducted in treatment-naïve patients with metastatic Merkel Cell Carcinoma (MCC). A total of 116 patients received 10 mg/kg infusions of Bavencio every 2 weeks until disease progression or unacceptable toxicity.

The primary efficacy endpoint was the durable response rate (DRR) defined as the proportion of treated patients with a response lasting at least 6 months. This endpoint was considered clinically relevant in the context of MCC as it incorporates the durability of response into the primary outcome measure.

At the time of the ad hoc analysis, all patients had been followed for at least 7 months with a median follow-up time of 13.7 months. The DRR was 27.6%. The Objective Response Rate (ORR) was 39.7% and the median duration of response (DOR) was 15.2 months.

Although complete responses were achieved in patients regardless of programmed death ligand-1 (PD-L1) status, a higher response rate was observed in patients with positive PD-L1 tumour expression (defined as having ≥ 1% PD-L1 staining on tumour cells) compared to patients with negative PD-L1 tumour expression (61.9% versus 33.3%, respectively). The median DOR also trended longer in the PD-L1 positive sub-group versus the PD-L1 negative sub-group (not yet reached versus 15.2 months).

The safety profile of avelumab in patients with metastatic MCC was consistent with clinical trials from previously authorized indications. No new safety signals were identified.

Overall, considering the improved durability of response with Bavencio compared to historical data using conventional chemotherapy, and the manageable safety profile, the benefit-risk was considered favourable for the treatment of patients with metastatic MCC for authorization under the Notice of Compliance with Conditions (NOC/c) policy.