1463 - Modified FOLFOX versus modified FOLFOX plus nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction – Moonlight, a randomized phase 2 trial of the German Gastric Group of the AIO.

Background

The majority of patients (pts) with gastroesophageal cancer present with inoperable or metastatic disease and there is a strong need for efficient and tolerable first-line (1L) treatment. Oxaliplatin-based regimens like FOLFOX have become one standard of care. However, median survival is still below 12 months. Results from trials using nivolumab plus ipilimumab treatment of subjects with advanced/metastatic GC and GEJ cancers demonstrated clinical activity, in pts whose tumors did or did not express PD-L1; in addition, nivolumab alone and in combination with ipilimumab demonstrated clinical benefits in various other tumor types. Based on this clinical experience, the AIO-STO-0417 trial (Moonlight) has been designed to evaluate the combination of chemotherapy with two checkpoint inhibitors in first-line therapy of pts with gastroesophageal adenocarcinoma.

Trial design

This is a prospective, multicenter, randomized, investigator-initiated phase II trial. Pts with Her2-negative, inoperable, advanced or metastatic gastric or esophagogastric junction cancer will be randomized 1:1 to 1L treatment with FOLFOX (Oxaliplatin 85 mg/m²; Leucovorin 400 mg/m²; 5FU 400 mg/m² on d1 of each treatment cycle and 5FU 2400 mg/m² continuous infusion over 44 hrs) every 2 weeks plus Nivolumab 240 mg every 2 weeks and Ipilimumab 1mg/kg every 6 weeks (Arm A) or FOLFOX alone (Arm B). Primary endpoint of the trial is progression-free survival based on the ITT population. Main secondary endpoints are overall survival, objective response rate, Safety and Quality of life (EORTC QLQ-C30). 118 pts (59 per arm) will be enrolled to provide 80% power for detecting an average HR of 0.68 using the log rank test at a one-sided type I error of 10%. At the date of submission (May 2019), 45 of planned 118 pts are randomized.

Clinical trial identification

NCT03647969.

Editorial acknowledgement

Legal entity responsible for the study

IKF Klinische Krebsforschung GmbH am Krankenhaus Nordwest.

Funding

Bristol-Myers Squibb.

Disclosure

S. Lorenzen: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Lilly; Advisory / Consultancy: Servier; Advisory / Consultancy: Sanofi; Advisory / Consultancy: MSD; Advisory / Consultancy: Celgene. T.O. Goetze: Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy: Shire; Advisory / Consultancy: Bayer; Advisory / Consultancy: Celgene; Advisory / Consultancy: Servier; Speaker Bureau / Expert testimony: MCI Group; Research grant / Funding (self), Research grant / Funding (institution): German Research Foundation. E. Goekkurt: Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck Serono; Travel / Accommodation / Expenses: Servier. T.J. Ettrich: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Sirtex Medical; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bayer; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Merck Serono; Travel / Accommodation / Expenses: Ipsen; Research grant / Funding (self): Baxalta. N. Homann: Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Advisory / Consultancy: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Celgene; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Merck. P.C. Thuss-Patience: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Nordic Bioscience; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Research grant / Funding (self): Novartis; Travel / Accommodation / Expenses: Teva; Travel / Accommodation / Expenses: Astellas Korea. H. Schmalenberg: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Research grant / Funding (self): Archigen. R.D. Hofheinz: Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb. S. Al-Batran: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Nordic Bioscience; Advisory / Consultancy: Merck Sharp and Dohme; Leadership role, Shareholder / Stockholder / Stock options: IKF Klinische Krebsforschung GmbH; Speaker Bureau / Expert testimony: AIO gGmbH; Speaker Bureau / Expert testimony: Forum für Medizinische Fortbildung; Speaker Bureau / Expert testimony: MCI group; Speaker Bureau / Expert testimony: promedicis; Research grant / Funding (self), Research grant / Funding (institution): Medac; Research grant / Funding (self), Research grant / Funding (institution): Hospira; Research grant / Funding (self), Research grant / Funding (institution): Sanofi; Research grant / Funding (self), Research grant / Funding (institution): German Cancer Aid; Research grant / Funding (self), Research grant / Funding (institution): German Research Foundation; Research grant / Funding (self), Research grant / Funding (institution): Federal Ministry of Education and Research of Germany; Research grant / Funding (self), Research grant / Funding (institution): Vifor Pharma. All other authors have declared no conflicts of interest.