First-line modified FOLFOX plus/minus nivolumab and Ipilimumab or FLOT plus nivolumab in advanced gastroesophageal adenocarcinoma: a phase II multi-cohort trial

This multi-cohort study evaluates whether dual immune checkpoint inhibition with nivolumab and ipilimumab in parallel or sequentially, or triplet chemotherapy with nivolumab can enhance efficacy as first-line therapy for advanced or metastatic gastroesophageal adenocarcinoma. Patients are randomized 1:1 to Arm A (mFOLFOX + nivolumab 240 mg every two weeks + ipilimumab 1 mg/kg every six weeks in parallel or Arm B (mFOLFOX). Subsequently, patients are randomized 1:2 to Arm A1 (identical to Arm A) or Arm A2 (three cycles of mFOLFOX followed by nivolumab + ipilimumab). In Arm C all patients receive FLOT + nivolumab. Primary endpoint is progression-free survival. Secondary endpoints include overall survival and objective response rate. Median progression-free survival (months) is: Arm A/A1, 5.8; Arm A2, 4.0; Arm B, 6.6 and Arm C, 7.0.Toxicity is manageable across all arms, with higher rates in arms receiving dual checkpoint inhibition. Here we show that chemotherapy with dual checkpoint inhibition in parallel increases toxicity without improving efficacy, while FOLFOX followed by immunotherapy is insufficient. FLOT with nivolumab appears feasible and shows promising efficacy. ClinicalTrials.gov number NCT03647969.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2026-02-27
DOI
https://doi.org/10.1038/s41467-026-69622-7
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

First-line modified FOLFOX plus/minus nivolumab and Ipilimumab or FLOT plus nivolumab in advanced gastroesophageal adenocarcinoma: a phase II multi-cohort trial

Maria Loose, Claudia Pauligk, Michael Bitzer, Claus Bolling et al.
Nature Communications
Cancer Immunotherapy and Biomarkers
article

First-line modified FOLFOX plus/minus nivolumab and Ipilimumab or FLOT plus nivolumab in advanced gastroesophageal adenocarcinoma: a phase II multi-cohort trial

Maria Loose, Claudia Pauligk, Michael Bitzer, Claus Bolling, S. Junge, Kim Barbara Luley, Tobias Dechow, Gunter Schuch, Thorsten Oliver Goetze, Udo Lindig, Stefan Angermeier, Salah-Eddin Al-Batran, Daniel Pink, Gunnar Folprecht, Sylvie Lorenzen, Ralf Dieter Hofheinz, Peter C. Thuss-Patience, Eray Goekkurt, Thomas Jens Ettrich, Volker Heinemann
article en

Abstract

This multi-cohort study evaluates whether dual immune checkpoint inhibition with nivolumab and ipilimumab in parallel or sequentially, or triplet chemotherapy with nivolumab can enhance efficacy as first-line therapy for advanced or metastatic gastroesophageal adenocarcinoma. Patients are randomized 1:1 to Arm A (mFOLFOX + nivolumab 240 mg every two weeks + ipilimumab 1 mg/kg every six weeks in parallel or Arm B (mFOLFOX). Subsequently, patients are randomized 1:2 to Arm A1 (identical to Arm A) or Arm A2 (three cycles of mFOLFOX followed by nivolumab + ipilimumab). In Arm C all patients receive FLOT + nivolumab. Primary endpoint is progression-free survival. Secondary endpoints include overall survival and objective response rate. Median progression-free survival (months) is: Arm A/A1, 5.8; Arm A2, 4.0; Arm B, 6.6 and Arm C, 7.0.Toxicity is manageable across all arms, with higher rates in arms receiving dual checkpoint inhibition. Here we show that chemotherapy with dual checkpoint inhibition in parallel increases toxicity without improving efficacy, while FOLFOX followed by immunotherapy is insufficient. FLOT with nivolumab appears feasible and shows promising efficacy. ClinicalTrials.gov number NCT03647969.

Nature CommunicationsVol. 17(1)
Goethe University Frankfurt (DE), Heidelberg University (DE), University Hospital Heidelberg (DE), LMU Klinikum (DE), Universitätsklinikum Tübingen (DE), Ravensburg University of Cooperative Education (DE), University Hospital Schleswig-Holstein (DE), Helios Hospital Bad Saarow (DE), Institute of Clinical Cancer Research (DE), University Cancer Center Hamburg (DE), University Hospital Frankfurt (DE), Jena University Hospital (DE), Praxis für Hämatologie und Onkologie (DE), Klinikum Ludwigsburg (DE), Agaplesion Markus Hospital (DE), University Hospital Ulm (DE), Frankfurt Cancer Institute (DE), University Hospital Carl Gustav Carus (DE), Technical University of Munich (DE), Charité - Universitätsmedizin Berlin (DE), University of Lübeck (DE)
Openalex Percentile: Top 39%
Cancer Immunotherapy and Biomarkers
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.