Background: Neoadjuvant CROSS regimen followed by adjuvant nivolumab or perioperative FLOT are current standards of care for patients with curable esophageal/ gastroesophageal (GEJ) junction adenocarcinoma. We hypothesized that adding avelumab to neoadjuvant chemo-radiation (CRT-A) before surgery can further improve outcomes. Methods: Patients with cT1-3 and N0/N1 M0 esophageal or GEJ adenocarcinomas eligible for curative surgery received weekly carboplatin and paclitaxel concurrently with radiotherapy (41.4 Gy in 23 fractions) and bi-weekly avelumab (5 doses). The trial had a run-in phase of 10 patients to evaluate feasibility and safety and a planned futility analysis after 15 patients have undergone surgery. The primary endpoint was pathological complete response (pCR) (Mandard criteria) by central pathology review, secondary endpoints were major histological response and survival outcomes. Using an A’hern single stage design for efficacy forty-seven patients were required to rule out a lower limit of a 20% pCR rate (p0) and to demonstrate an increase to a 40% pCR rate (p1), with 90% power and significance level α=0.05. Tissue, blood, and stool samples were collected for corelative analysis. Results: 48 patients were enrolled between Sept 2019 to Oct 2022 across seven Australian sites. Median age 65 [44-81], 95% were male (n=45), with majority of cancers being esophageal/GEJ type I (n = 35), with GEJ type II (n = 13). Forty-seven (97%) patients completed CRT -A and 46 (95%) had surgery. CRT-A was well tolerated, with two patients having > grade 2 adverse event of interest in the form of myocarditis attributed to avelumab. Notable toxicities included grade 2-4 myocarditis (4%), anastomotic leak (4%), infection (6%) and diarrhoea (6%). In 44 evaluable patients, pCR was 23%. MHR was 58.3% (95% CI, 43.3%-72.1%), complete or near complete response (Tumor Regression Grade 1-2) was 31%. Overall, 1-yr disease free survival was 83.8% and OS was 91.2%. 1-yr disease free survival was 91.7% for patients with MHR vs 73.3% without MHR, p=0.20. Conclusions: Combining avelumab with neoadjuvant CRT is feasible in patients with acceptable tolerability in locally advanced esophageal/ GEJ adenocarcinoma. Avelumab with CRT is active however observed pCR rate does not represent a signal of substantial improvement compared to historical controls. Exploratory analysis suggests improved outcomes in patients with optimal tumour regression after neoadjuvant CRT-A. Exploratory biomarker work to corelate with outcomes is underway. Clinical trial information: ACTRN12619000288123.