Oral TGF-beta Receptor I Inhibitor Vactosertib in SOC Chemoradiotherapy for Esophageal Adenocarcinoma

Esophageal adenocarcinoma (EAC) is an aggressive malignancy with limited effective treatment options. In localized EAC (clinical stages II and III), the standard of care is pre-operative concurrent chemoradiation (CRT) followed by surgical resection, which results in pathologic complete response (pCR) in approximately 20% of participants, but with high rates of post-operative recurrence. It was recently discovered that EACs are driven by signaling through TGFβ Receptor I (TGFβRI), and in vivo models of EAC show tumor reduction by targeting this pathway with a novel small molecule inhibitor of TGFβRI called vactosertib. In this study, participants who have locally advanced EAC will be treated with vactosertib before and after standard of care chemoradiation to take advantage of natural windows of opportunity during which participants are being planned for their standard of care treatments.