1185MO Activity and safety of avelumab alone or in combination with cabozantinib in patients with advanced high grade neuroendocrine neoplasias (NEN G3) progressing after chemotherapy. The phase II, open-label, multicenter AVENEC and CABOAVENEC trials

NEN G3 are rare tumors with poor prognosis and have no established 2nd- line therapy. The role of immune checkpoint blockade in these aggressive tumors remains unclear. We report the final analysis of the phase II AVENEC study on the effect of anti-PDL1 therapy with avelumab (AVE, 10 mg/kg iv Q2W) in 60 patients (pts) with highly proliferative neuroendocrine tumors (NET) G3 (N=22) or undifferentiated neuroendocrine carcinomas (NEC, N=38) of any origin, progressing after ≥ 1 chemotherapy (excluding Merkel cell and small cell lung cancer), and compare it with the interim analysis of 19 progressive NEN G3 pts treated with AVE (800 mg iv Q2W) in combination with cabozantinib (CAB, 40 mg/d po) from the ongoing phase II CABOAVENEC study. AVENEC: Best overall response (iRECIST) of AVE was a partial response (PR) in 3 (5%) and a stable disease (SD) in 9 (15%) pts, with a disease control rate (DCR) at 16 wks of 15 % (1 PR, 8 SD), and a median duration of response of 18.2 wks. 6 pts (10 %) achieved SD or PR for > 24 wks, and 2 pts for > 52 wks. Response was similar regardless of differentiation, Ki67 or primary localization. After a median follow up (mFU) of 27.9 wks, only 11 (18 %) pts were still alive with a median overall survival (mOS) of 21.3 wks (CI 15.0–nr), and a median progression free survival (mPFS) of 8.1 wks (CI 6.1-8.1). AVE was well tolerated with no drug related withdrawals and a stable quality of life (EORTC QLQ-C30). CABOAVENEC: preliminary data from 19 pts (12 NET G3, 7 NEC) treated with AVE + CAB show a PR in 4, SD in 5, and progress in 5 pts (5 not yet evaluable). mPFS was 48.1 wks (CI 15,9-nr) with a DCR at 16 wks of 42 % (5/12). After a mFU of 29.1 wks, 17 (85%) pts are alive, with 2 pts still on treatment for > 1 yr. Adverse events of the combination therapy were as expected and manageable. Only a minority of 10-15% of heavily pretreated NEN G3 pts benefit from AVE monotherapy, which is very well tolerated. However, preliminary data suggest that the combination of AVE + CAB might be more effective in a higher percentage of pts and could therefore be a promising option for 2nd -line therapy for these aggressive tumors.