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

Inclusion Criteria

• 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)