A multi-cohort phase II study of durvalumab plus tremelimumab for the treatment of patients (pts) with advanced neuroendocrine neoplasms (NENs) of gastroenteropancreatic or lung origin: The DUNE trial (GETNE 1601)

Abstract

BackgroundImmune checkpoint blockade (ICB) has demonstrated limited activity in advanced NENs mainly due to the background biology of these “cold” neoplasms, with low tumor mutational burden, expression of PD-L1 and lymphocyte infiltration. Targeting both PD-L1 and CTLA-4 may increase the efficacy of ICB in NENs and revert the intrinsic resistance to this therapeutic approach.MethodsPts were recruited in four cohorts (C1-4): typical/atypical lung carcinoids (C1), G1/2 gastrointestinal (C2), G1/2 pancreatic (C3) and G3 NENs of gastroenteropancreatic origin (C4). All pts were included after progression to standard therapies for each C. Pts received durvalumab (D) 1500 mg up to 13 cycles and tremelimumab (T) 75 mg up to 4 cycles, every 4 weeks. Primary objective was 9-month (m) clinical benefit rate (CBR) for C1-3 and 9-m overall survival rate (OS) for C4. Assuming a 9mCBR P0/1 of 30%/50% for C1-3, and 9mOS P0/1 of 13%/23% for C4, (α=0,05 and 80% power) 28 pts in C1-3 and 30 pts in C4 were needed.