ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer (HER2)

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)