A Dose Finding Study of ZW49 in Patients With HER2-Positive Cancers

Inclusion Criteria: * Pathologically-confirmed diagnosis of breast cancer, gastroesophageal adenocarcinoma (GEA), or other HER2-expressing cancer with evidence of locally advanced (unresectable) and/or metastatic disease. * Dose-escalation (Cohort 1): HER2-high advanced solid tumors * Expansion (Cohort 2): HER2-high breast cancer * Expansion (Cohort 3): HER2-high GEA * Expansion (Cohort 4): HER2-high other non-breast and non-GEA cancers * Progressive disease that has progressed on or been refractory to all standard of care. Patients who were intolerant to or ineligible for standard therapy may be eligible if the reasons are carefully documented and approval is provided by the sponsor medical monitor * Patients with HER2-high breast cancer must have received prior treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1) * Patients with HER2-high GEA must have received prior treatment with trastuzumab * Sites of disease assessible per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 * Dose-escalation: measurable or non-measurable disease * Expansion: measurable disease * ECOG performance status score of 0 or 1 * Adequate organ function * Adequate cardiac left ventricular function, as defined by a LVEF \>/= institutional standard of normal Exclusion Criteria: * History of myocardial infarction or unstable angina within 6 months prior to enrollment, troponin levels consistent with myocardial infarction, or clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension, or any history of symptomatic congestive heart failure (CHF) * Clinically significant infiltrative pulmonary disease not related to lung metastases * Active hepatitis B or hepatitis C infection or other known chronic liver disease * Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with exception of patients with Gilbert's Syndrome, asymptomatic gall stones, liver metastases, or stable chronic liver disease per investigator assessment) * Known history of human immunodeficiency virus (HIV) infection * Brain metastases: Untreated CNS metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks of start of study treatment. Stable, treated brain metastases are allowed (defined as patients who are off steroids and anticonvulsants and are stable for at least 1 month at the time of screening). * Known leptomeningeal disease (LMD)