TPS4166 Background: The tumor stroma is increasingly acknowledged to harbor tumor-promoting properties. Recently, we found that stroma activity measured by serum ADAM12 predicts response to chemoradiation in esophageal adenocarcinoma (Veenstra et al., Oncogenesis, 2018). Preclinically, the esophageal adenocarcinoma stroma was found to produce interleukin 6, which causes epithelial-to-mesenchymal transition of tumor cells. These mesenchymal tumor cells have a poor response to chemoradiation (Ebbing et al., PNAS, 2019). Therefore, stroma-derived interleukin 6 provides a potential new target to improve the treatment of esophageal adenocarcinoma. Tocilizumab is an interleukin 6 receptor inhibitor clinically used in rheumatoid arthritis and cytokine-release syndrome. In this phase II proof-of-concept clinical trial, we aim to demonstrate that stroma-targeting by tocilizumab in esophageal adenocarcinoma patients with highly activated stroma increases efficacy of chemoradiation measured by pathological response according to the Mandard criteria. Methods: BASALT is a multi-center, randomized, open-label phase II proof-of-concept clinical trial in patients with surgically resectable adenocarcinoma of the esophagus or gastroesophageal junction (NCT04554771). To assess efficacy of tocilizumab in addition to chemoradiation, 48 patients will be grouped for serum ADAM12 level with a cutoff of 203 pg/mL. Patients are then randomized in a 1:1:1:1 ratio to receive three cycles of tocilizumab every two weeks in addition to paclitaxel, carboplatin and radiation (Table). The sample size is based on the rule-of thumb estimate of 12 patients per arm. Tocilizumab will be given intravenously at a dose of 8 mg/kg with a maximum of 800 mg per dose. Efficacy will be assessed by pathological response to chemoradiation according to the Mandard criteria. Secondary endpoints are overall and progression free survival, safety and toxicity, feasibility and efficacy of interleukin 6 inhibition with serum interleukin 6 levels, immunohistochemistry and RNA-sequencing. Currently, 28 out of the 48 planned patients have been enrolled. Clinical trial information: NCT04554771. [Table: see text]