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

Prior treatment

• Severe cardiac arrhythmias, requiring treatment, symptomatic congestive heart failure, myocardial infarction within 28 days prior to first dose, or unstable angina.
• Active infection requiring systemic therapy within 14 days before the first dose
• Brain lesion requiring immediate local therapy

Other illness

• Another active malignancy within 2 years except basal cell skin cancer and carcinoma in situ treated curatively
• Active or chronic liver disease
• Leptomeningeal disease
• Uncontrolled seizures

Lab values

• Corrected QT interval (QTc) of \>470 milliseconds (ms) females or \>450 ms for males by Fridericia (QTcF)

• 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