Abstract 1188TiP
Background
Grade 3 (G3) NENs comprise a subgroup of neuroendocrine neoplasms with a high proliferative index and aggressive behaviour. Median overall survival (OS) of patients (pts) with advanced disease is up to 12 months with the best available platinum-based chemotherapy. Therefore, there is a great need for more effective therapeutic options in this setting. G3 NENs are highly mutated tumors with increased PD-L1 expression, which is strongly associated with response to immunotherapy. The aim of this study is to assess safety and efficacy of adding immune check-point inhibitors to standard chemotherapy in pts with advanced chemo-naïve G3 NENs.
Trial design
NICE-NEC is a non-randomized open-label phase II trial recruiting pts with metastatic or unresectable G3 NENs of gastroenteroenpathic (GEP) or unknown (UK) origin across 12 Spanish centers from the Spanish Taskforce of Neuroendocrine Tumors (GETNE). Study treatment comprises an initial induction phase with 6 cycles of Nivolumab 360 mg / Carboplatin AUC 5 / Etoposide 100 mg/m2/d administered intravenously (IV) on days 1/1/1-3, respectively, every 21; followed by maintenance treatment with Nivolumab 480 mg IV every 4 weeks, up to 2 years or disease progression, whatever occurred first. Key inclusion criteria are histologically confirmed non-resectable or stage IV G3 (Ki-67>20%) NENs, GEP or UK primary, measurable disease, no prior systemic treatment, adequate organ function and ECOG ≤2. Primary objective is to determine one-year OS rate. Secondary objectives: objective response rate, progression free survival (PFS), and duration of response according to RECIST 1.1, safety and exploratory assessment of predictive and prognostic biomarkers. The sample size was calculated with 80% power to test H0 (1-year OS rate of 0.5), requiring 38 pts, yielding a two-sided type I error rate of 5% when the true one-year OS rate is 0.72. NICE-NEC accrual started on October 2019 and is currently actively recruiting patients. 16 pts have been enrolled to date, the last patient of the last visit is expected for 2Q 2022.
Clinical trial identification
EudraCT: 2019-001546-18.
Editorial acknowledgement
Legal entity responsible for the study
Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE).
Funding
Bristol-Myers Squibb.
Disclosure
M.C. Riesco Martínez: Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Bayer; Advisory/Consultancy: Novartis; Travel/Accommodation/Expenses: Servier; Non-remunerated activity/ies: Incyte Bioscience. J. Capdevila: Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (self): Ipsen; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Advanced Accelerator Applicat; Advisory/Consultancy: Amgen; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Merck Serono; Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (self), Research grant/Funding (institution): Advance Accelerator App. V. Alonso: Advisory/Consultancy: Amgen; Speaker Bureau/Expert testimony: Merck Serono; Advisory/Consultancy: Roche; Speaker Bureau/Expert testimony: Sanofi Genzyme; Advisory/Consultancy: Servier; Advisory/Consultancy: Bayer; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Novartis. A. Teule: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AAA; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca. E. Grande: Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role: IPSEN; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eusa Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi-Genzyme; Advisory/Consultancy, Speaker Bureau/Expert testimony: Adacap; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role: Lexicon; Advisory/Consultancy, Speaker Bureau/Expert testimony: Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role: Astellas; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role: AstraZeneca; Leadership role: MTEM/Threshold; Advisory/Consultancy, Leadership role: GETNE; Advisory/Consultancy: ENETS; Advisory/Consultancy: GETHI. P. Jimenez-Fonseca: Travel/Accommodation/Expenses: IPSEN; Advisory/Consultancy: AAA; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: LEOpharma; Speaker Bureau/Expert testimony: HRApharma. M. Benavent: Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis. T. Alonso Gordoa: Advisory/Consultancy, Speaker Bureau/Expert testimony, Non-remunerated activity/ies: IPSEN; Advisory/Consultancy, Speaker Bureau/Expert testimony, Non-remunerated activity/ies: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Roche; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy, Research grant/Funding (institution): Janssen-Cilag; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): EISAI; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): GSK-Novartis; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Nektar Therapeutics; Non-remunerated activity/ies, Member: Spanish Germ Cell Tumors Board; Advisory/Consultancy: SEOM. A. Custodio: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): IPSEN; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: AAA; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Non-remunerated activity/ies: Getne; Non-remunerated activity/ies: Enets. C. Hierro Carbó: Speaker Bureau/Expert testimony: Ignytia; Speaker Bureau/Expert testimony: Lilly; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Merck; Research grant/Funding (institution): Bayer. C. López: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AAA; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca. I. Sevilla García: Advisory/Consultancy: Ipsen; Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Pfizer; Speaker Bureau/Expert testimony: PharmaMar; Advisory/Consultancy: Amgen; Speaker Bureau/Expert testimony: Bayer; Speaker Bureau/Expert testimony: AAA. R. García-Carbonero: Advisory/Consultancy, Speaker Bureau/Expert testimony: AAA; Advisory/Consultancy, Speaker Bureau/Expert testimony: Advanz Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Non-remunerated activity/ies: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: HMP; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ipsen; Speaker Bureau/Expert testimony, Leadership role, Research grant/Funding (institution): Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Midatech Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): PharmaMar; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution), Non-remunerated activity/ies: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi and Servier; Research grant/Funding (institution): ARMO Biosciences; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pharmacyclics; Research grant/Funding (institution): Boston biomedicals; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Bristo-Myers-Squibb; Research grant/Funding (institution): Boehringer; Research grant/Funding (institution): Sysmex; Research grant/Funding (institution): Gilead Science; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Adacap; Research grant/Funding (institution): VCN; Research grant/Funding (institution): Lilly; Leadership role, Non-remunerated activity/ies: GETNE; Leadership role, Non-remunerated activity/ies: ENETS; Leadership role, Non-remunerated activity/ies: SAG-O EMA; Non-remunerated activity/ies: EORTC; Non-remunerated activity/ies: ASCO; Non-remunerated activity/ies: ESMO; Non-remunerated activity/ies: SEOM; Non-remunerated activity/ies: TTD; Non-remunerated activity/ies: GEMCAD.