Background: The outcome of patients (pts) with adenocarcinomas of stomach and esophagogastric junction (GEJ) remains unsatisfactory (5-year survival rates of 24-84%), whereby surgical resection is considered as cornerstone of the curative treatment for pts with early stage esophageal adenocarcinoma (EGA), however, it is associated with mortality, morbidity and an impact on the patient’s quality of life. Recent investigations showed that in locally advanced stage EGA surgery with neoadjuvant chemoradiotherapy (CROSS trial) is beneficial over surgery alone. Further benefit was achieved for locally advanced EGA by perioperative treatment with FLOT acc. to FLOT4- trial data. Immuno-oncology (IO) therapy by using checkpoint inhibitors is approved in the palliative and adjuvant EGA situation. In this trial we aim for the organ preservation treatment of EGA pts with a combination of the anti PD-L1 antibody durvalumab- FLOT - and chemoradio-therapy. Methods: This is a multicenter, single arm, open-label, phase II trial including a total of 32 pts with T1-T2N0 EGA (including GEJ) with indication for radical surgery. Enrolled pts will receive immunotherapy with durvalumab (1500 mg Q4W) in parallel to 2 cycles FLOT (50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 calcium folinate and 2600 mg/m2 5FU, Q2W) induction followed by 3 cycles of mFOLFOX (85 mg/m2 oxaliplatin, 200 mg/m2 calcium folinate, 400 mg/m2 5FU bolus and 1600 mg/m2 5FU over 48h, Q2W) plus concomitant radiation (25 daily fractions with 2.0 Gy = Σ50Gy). 8 weeks after last treatment, pts will undergo tumor assessment by esophagogastroduodenoscopy with biopsies, endoscopic ultrasonography, and CT- or MRI-scans. Surgical resection would be offered only to pts in whom a locoregional persistence is confirmed. Pts with complete remission will enter the maintenance phase and will receive durvalumab monotherapy (1500 mg, Q4W) for a maximum of 12 cycles accompanied by regular tumor re-evaluation. Primary endpoint is the rate of cCR/pCR at time of re-evaluation. Secondary endpoints include rate of cCR/pCR at 1, 2 and 3 years, rate of salvage surgery, 90 day and 1 year mortality after start of treatment, safety and quality of life. In this exploratory trial a cCR/pCR rate of ≥75% would indicate that the study treatment should be further investigated, whereas a rate < 55% indicates no further investigation. First patient was enrolled on 2023-08-28. Currently one patient is recruited. Clinical trial information: NCT05713838.