Durvalumab plus Tremelimumab for the Treatment of Patients (pts) with Advanced Neuroendocrine Neoplasms (NENs) of Lung or Gastroenteropancreatic (GEP) Origin. A Phase II Multicohort Trial (DUNE Trial / GETNE 1601)
Introduction: Immuno check-point inhibitors development in grade 1-2 NENs is limited by low mutation tumor load and PD-1/PDL-1 expression. The combination of an PDL-1 and CTLA-4 inhibitors could increase the probability of success in this setting. In high grade NENs the rational for immunotherapy is stronger based on experiences in small cell lung cancer.
Aim(s): This prospective, multi-center, open label, phase II study (EudraCT:2016-002858-20) will evaluate the efficacy and safety of Durvalumab plus Tremelimumab within four different cohorts: Well-moderately differentiated lung NENs (1), grade 1-2 gastrointestinal NENs (2), grade 1-2 pancreatic NENs (3) and grade 3 GEP NENs (4).
Materials and methods: Pts included in the trial must have progressed to all standard therapies in each setting for lung and GEP grade 1-2 NENs up to 4 prior lines. For pts included in cohort 4, progression to platinum-based chemotherapy is mandatory. All pts will receive durvalumab 1500 mg every 28 days for 12 months, and tremelimumab 75 mg Q4W up to 4 doses/cycles. Retreatment is allowed after progression in the follow-up period. The primary endpoint for cohorts 1-3 is disease control rate at 9 months including the percentage of pts achieving complete or partial response, or stable disease according to RECIST v1.1; for cohort 4 the primary endpoint will be median overall survival. These endpoints will be assessed by investigators and confirmed by central radiological review. Secondary endpoints include median progression-free survival, safety and tolerability and a wide panel of biomarkers in blood and tumor samples.
Conference: 15th Annual ENETSConcerence (2018)
Presenting Author: Hernando-Cubero J
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