Ivonescimab in combination with chemotherapy in advanced or metastatic gastric cancer (GC) or esophagogastric junction cancer (EGJC): The UCGI 52 - GRACIE trial.

BACKGROUND: While the addition of Ivonescimab to chemotherapy has demonstrated promising results in non-small cell lung cancer compared with chemotherapy alone, its efficacy as a first- or second-line treatment in advanced/metastatic gastric cancer remains to be established. AIMS: GRACIE aims to evaluate the efficacy and safety of Ivonescimab combined with FOLFOX chemotherapy as first-line treatment (Arm-1) or as second-line when combined with paclitaxel or irinotecan or FOLFIRI following progression (Arm-2), in patients with advanced/metastatic gastric cancer and esophageal adenocarcinoma, regardless of actionable targets' presence (PD-L1/HER2/CLDN-18.2). METHODS: This multicenter, two-arm, non-randomized, open-label exploratory phase II study is recruiting 88 patients, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, over 18 French centers. The primary objective is the Objective Response Rate (ORR) after central review according to RECIST v1.1 in HER2- and CLDN-18.2-negative, treatment-naïve patients (Arm-1) and patients with a single previous line for advanced disease, regardless of biomarkers expression (Arm-2). Secondary objectives are investigator-assessed ORR, Duration-of-Response, Progression-Free Survival, Overall Survival, time to ECOG performance status deterioration, Safety and Quality-of-life. DISCUSSION: GRACIE will provide crucial information about Ivonescimab plus chemotherapy regimens efficacy either as a first- or second-line treatment in molecularly defined advanced/metastatic gastric and esophageal adenocarcinomas to inform future phase III trials. TRIAL REGISTRATION: EU-CTIS: 2025-520694-39-00, ClinicalTRials.gov: NCT06846346.