Clinical Research Directory

Inclusion Criteria: Phase 1a Monotherapy Dose Escalation and Exploration: * Pathologically documented advanced stage solid tumor * Progressed following all standard treatment or not appropriate for standard treatment * HER2 mutation, HER2 amplification or HER2 positive based on local testing Phase 1b Monotherapy * Pathologically documented unresectable and/or metastatic non-squamous NSCLC * HER2 mutation identified by tissue (fresh or archival) or ctDNA. Local testing for up to 20 patients the remainder centrally confirmed. * Measurable disease * No known epidermal growth factor receptor (EGFR), ROS1, anaplastic lymphoma kinase (ALK), or BRAF V600E mutation * Progressed after receiving at least 1 prior systemic therapy including a platinum-based chemotherapy with or without immunotherapy, or not appropriate for standard treatment. * No prior HER2 tyrosine kinase inhibitor. Prior HER2 directed antibodies or anti-body drug conjugates are allowed * No limit on prior number of therapies Phase 1a Combination with T-DXd * Pathologically documented advanced stage NSCLC * Progressed after receiving at least 1 prior systemic therapy. * HER2 mutation based on local/historical testing of tissue or circulating tumor DNA * No known EGFR, ROS1, ALK, or BRAF V600E mutation * No prior T-DXd * No clinically severe pulmonary compromise * No limit on prior number of therapies Phase 1a Combination Breast Cancer * Documented HER2 positive (Immunohistochemical \[IHC\] 3+ or IHC2+/in situ hybridization (ISH+) breast cancer * Must have previously received trastuzumab, a taxane, and T-DXd (if available and appropriate) in the metastatic setting. * No limit on prior number of therapies * No prior T-DM1 All Phases * Eastern Cooperative Oncology Group performance status of 0-1 * Left ventricular ejection fraction ≥ 50% * Platelet count ≥ 100 x 109/L * Hemoglobin ≥ 8.5 g/dL * Absolute neutrophil count ≥1.0 x 109/L * Total bilirubin \< 1.5 times upper limit of normal range (ULN), except for patients with Gilbert's syndrome * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) \< 3 times ULN. In the setting of liver metastases \< 5 times ULN. * Creatinine clearance ≥ 60 mL/minute Exclusion Criteria All Phases: * Severe cardiac arrhythmias, requiring treatment, symptomatic congestive heart failure, myocardial infarction within 28 days prior to first dose, or unstable angina. * Another active malignancy within 2 years except basal cell skin cancer and carcinoma in situ treated curatively * Active or chronic liver disease * Active infection requiring systemic therapy within 14 days before the first dose * Brain lesion requiring immediate local therapy * Leptomeningeal disease * Uncontrolled seizures * Corrected QT interval (QTc) of \>470 milliseconds (ms) females or \>450 ms for males by Fridericia (QTcF)