Multicenter phase 2 trial of avelumab for high-grade neuroendocrine neoplasia progressive after chemotherapy

Neuroendocrine neoplasias grade 3 are rare tumors with poor prognosis and no established second-line therapy. The role of immune checkpoint blockade in these aggressive tumors remains unclear. The multicenter phase 2 AveNEC trial in Germany evaluated avelumab (10 mg/kg IV Q2W) in 60 patients with well-differentiated high-grade neuroendocrine tumors or poorly differentiated neuroendocrine carcinomas progressing after one or more lines of chemotherapy. The disease control rate at 16 weeks was 15% (3 PR, 6 SD) with a median duration of response of 4.3 months. The median progression-free survival was 1.9 months, and the median overall survival was 6.6 months, with one- and two-year survival rates of 33% and 17%, respectively. Responders had longer median overall survival than non-responders (30.2 versus 4.8 months). Avelumab was well tolerated. The authors conclude that among patients with progressive high-grade neuroendocrine neoplasia, avelumab provided disease control with significant clinical benefit in 15% of patients.