• Patients must have pathologically or cytologically confirmed esophageal, gastric or gastroesophageal junction (GEJ) adenocarcinoma by the enrolling institution.

• Patients must have esophageal, gastric or GEJ adenocarcinoma with HER2 overexpression and/oramplification as determined by immunohistochemistry (IHC 3+) or fluorescent in situ hybridization (FISH+ as defined as HER2:CEP17 ratio ≥2.0 if IHC 2+). No central testing will be required. The testing can be performed on archival tissue that is less than 6 months old. If archival tissue is more than 6 months old, a new biopsy must be obtained to confirm HER2 status prior to enrollment.

• Patients may have received no prior chemotherapy or be treatment naïve for stage IV disease. Patients may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if more than 6 months have elapsed between the end of adjuvant therapy and expected date of treatmentstart on this study. Patients who have received maintenance nivolumab after chemoradiation and surgery would be eligible as long as the last dose of nivolumab was more than 3 months from thedate of expected date of treatment start on this study.

• Patients must have measurable disease per RECIST v1.1.

• Patients must not have active decompensated cardiomyopathy and must have a normal LVEF (≥ 53%). If a patient has a borderline LVEF (40-52%), they may be considered after consultation with cardiology and study PI.

• ECOG performance status 0 or 1.

• Demonstrate adequate organ function as outlined in protocol.

• Female patients of childbearing potential should have a negative urine or serum pregnancy within 72hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

• Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 2 years.

• Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

• Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system- (CNS-) directed therapy shows no evidence of progression at 4-6 weeks after treatment.

• Ability to understand and the willingness to sign a written informed consent document