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

Background

NEN G3 are rare tumors with poor prognosis and have no established 2^nd- line therapy. The role of immune checkpoint blockade in these aggressive tumors remains unclear.

Methods

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.

Results

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.

Conclusions

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 2^nd -line therapy for these aggressive tumors.

Clinical trial identification

NCT03352934 and NCT05289856.

Editorial acknowledgement

Legal entity responsible for the study

University Medical Center of the Johannes Gutenberg-University Mainz, Germany.

Funding

Merck Healthcare KGaA and Ipsen.

Disclosure

M.M.M. Weber: Financial Interests, Personal, Invited Speaker: Ipsen, Novartis, Lilly; Financial Interests, Personal, Advisory Board: Ipsen, Novartis, Lilly; Financial Interests, Institutional, Funding, Funding for CaboAveNEC Study: Ipsen; Financial Interests, Institutional, Funding, Funding for AveNEC and CaboAveNEC Study: Merck; Financial Interests, Institutional, Funding: Fresenius. L. Apostolidis: Financial Interests, Personal, Speaker, Consultant, Advisor: Ipsen Novartis; Financial Interests, Institutional, Principal Investigator: Camurus. S. Krug: Financial Interests, Personal, Advisory Board: Ipsen, AAA and Advanz Pharma; Financial Interests, Personal, Invited Speaker: Ipsen, AAA and Advanz Pharma. A. Rinke: Financial Interests, Personal, Advisory Board: Novartis, Ipsen, Advanz, Esteve; Financial Interests, Personal, Invited Speaker: IPSEN, Novartis, Advanz, Falk; Financial Interests, Institutional, Research Funding: IPSEN, Novartis, itm solution. B. Gruen: Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Dr. Rönsberg GmbH ; Financial Interests, Personal, Other: Sanofi Genzyme. P. Michl: Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Institutional, Research Funding: Ipsen. D. Wagner: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Janssen; Financial Interests, Institutional, Research Funding: Roche and BMS. P.R. Galle: Financial Interests, Personal, Speaker, Consultant, Advisor: Bayer, Boston Scientific, AstraZeneca, Adaptimmune, BMS, Eisai, MSD, Sirtex, Lilly, Roche, Guerbet, Ipsen. C. Fottner: Financial Interests, Personal, Invited Speaker: Ipsen. All other authors have declared no conflicts of interest.