Study on Neratinib with Chemotherapy, Trastuzumab, and Pembrolizumab for HER2 Gastroesophageal Cancer

Inclusion Criteria

• Have a confirmed diagnosis of esophageal, gastric, or gastroesophageal junction (GEJ) adenocarcinoma.
• The cancer must show HER2 overexpression, confirmed by specific lab tests.
• May not have received prior chemotherapy for stage IV disease, or if previously treated, it must have been more than 6 months ago.
• Must have measurable cancer according to standard criteria.
• Must not have severe heart problems and should have a normal heart function test.
• Be in good overall health with an ECOG performance status of 0 or 1, meaning fully active or restricted in physically strenuous activity but ambulatory.
• Must have adequate organ function based on specific medical tests.
• Women of childbearing potential must have a negative pregnancy test before starting treatment and agree to use effective birth control during the study and for 120 days after the last dose.
• Men must agree to use effective contraception during the study and for 120 days after the last dose.
• Participants with treated brain metastases are eligible if follow-up scans show no progression.
• Must be able to understand and sign a written informed consent document.

Exclusion Criteria

• Currently participating in another study or have used an investigational treatment within 4 weeks before starting this study.
• Have had prior treatment for metastatic disease or have not recovered from side effects of previous treatments, except for hair loss or mild thyroid issues.
• Have active brain metastases or cancer in the brain lining.
• Have an active autoimmune disease requiring treatment in the past 2 years, except for replacement therapies.
• Have a diagnosis of immunodeficiency or are on chronic steroid therapy.
• Have a history of lung inflammation requiring steroids or current lung issues.
• Have an active infection needing treatment.
• Have significant nerve damage.
• Have any condition that might interfere with the study or is not in the best interest of the patient to participate.
• Have psychiatric or substance abuse disorders affecting study participation.
• Are pregnant, breastfeeding, or planning to conceive during the study and for 120 days after.
• Have had a COVID-19 infection within 90 days before eligibility confirmation or unresolved symptoms.
• Have significant heart disease or abnormal heart rhythms.
• Have a chronic gastrointestinal disorder with diarrhea as a major symptom.