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

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)