Avelumab

Avelumab is a human antibody approved for Merkel cell carcinomasince September 2017, which specifically binds to a protein expressed by the tumour cells, the "programmed cell death ligand 1", or PD-L1 for short. By binding to the PD-L1 protein, Avelumab prevents tumour cells from using PD-L1 themselves to protect themselves from T cells. In a process known as antibody-dependent cellular cytotoxicity (ADCC), Avelumab appears to support natural killer cells with regard to their oncogenic effectiveness.

A pivotal study of the anti-PD-L1 antibody Avelumab in 88 patients shows clinically significant tumor response in pretreated, metastatic Merkel cell carcinoma (MCC)

The planned primary evaluation of the study showed an objective response rate (ORR) of 31.8% (28 of 88 patients; 95.9% AI: 21.9 - 43.1%†) and a controllable safety profile in patients with metastatic Merkel cell carcinoma (MCC) treated with Avelumab in the second or later therapy line. A rapid and sustained tumor response was observed: 78.6% of patients (22 out of 28) responded within seven weeks of treatment initiation and 82.1% of patients (23 out of 28) were still responding at the time of evaluation. In this study, 8 patients (9.1%) achieved a full remission (tumor no longer detectable) and 20 patients (22.7%) achieved partial remission. A tumor response was observed in the patients regardless of their status of certain biomarkers (PD-L1 and Merkel cell polyomavirus). The progression-free survival rate at 6 months was 40% (95% AI: 29 - 50%, Kaplan-Meier estimate). The early data also showed an overall survival rate at 6 months of 69% (95% CI: 58 - 78%) and a median overall survival of 11.3 months (7.5 - 14.0 months).

Patients were administered avelumab i.v. at a dose of 10 mg/kgKG every 2 weeks. Currently, there is an approval for a fixed dose of 800 mg every 2 weeks. Due to infusion reactions, premedication with paracetamol and an antihistamine is recommended for the first 4 doses.

Bavencio®

Following positive completion (D`Angelo SP et al. 2017) of the pivotal study (JAVELIN), Avelumab has been approved for first-line treatment of metastatic Merkel cell carcinoma since September 2017.

S. a. Avelumab/Internal Medicine

1. Frohm ML et al (2016) Recurrence and Survival in Patients With Merkel Cell Carcinoma Undergoing Surgery Without Adjuvant Radiation Therapy to the Primary Site. JAMA Dermatol 152:1001-1007.
2. Garneski KM et al (2007) Merkel cell carcinoma adjuvant therapy: current data support radiation but not chemotherapy. J Am Acad Dermatol 57: 166-169
3. Kaufman HL et al(2016) Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol 17:1374-1385.
4. Lemos B et al (2010) Pathologic Nodal Evaluation Improves Prognostic Accuracy in Merkel Cell Carcinoma: Analysis of 5,823 Cases as the Basis of the First Consensus Staging System for this Cancer. Journal of the American Academy of Dermatology. 63:751-761.