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

Inclusion Criteria: * Subjects must have histologically or cytologically confirmed poorly differentiated or Grade 3 adenocarcinoma of the esophagus or gastroesophageal junction, clinical stage II or III and must be appropriate for standard of care preoperative therapy with concurrent chemoradiotherapy with carboplatin and paclitaxel or FOLFOX OR with FLOT as per standard of care. Clinical staging appropriate: * cT2 N0 with high-risk lesions including lymphovascular invasion, tumors ≥ 3cm in size, or poorly differentiated histology, or * cT1b-cT2, N+, or * cT3-cT4a, any N * Subjects must be deemed a potential surgical candidate by a thoracic surgeon, surgical oncologist, or surgeon who is qualified to perform an esophagectomy * Subjects must NOT have received prior chemotherapy, immunotherapy, or radiation therapy for management of this malignancy (prior ablations or localized therapies for Barrett's metaplasia are acceptable) * Age ≥18 years. Because no dosing or adverse event data are currently available on the use of vactosertib in subjects ≤18 years of age, children are excluded from this study. * ECOG Performance status ≤2 * Subjects must have adequate organ and marrow function as defined below: * Serum total bilirubin \<2 mg/dl. If known Gilbert syndrome, total bilirubin must be \<3mg/dl * AST (SGOT) ≤ 2.5 X institutional upper limit of normal * ALT (SGPT) ≤ 2.5 X institutional upper limit of normal * Serum Creatinine ≤ 1.5 X institutional upper limit of…