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

The goal of this clinical trial is to test ELVN-002 in people with cancers that ha an abnormal HER2 gene. The main question the trial aims to answer is if ELVN-002 is safe and tolerable at different doses. A second main question is to evaluate the concentration of ELVN-002 in the blood at different doses and to see how this correlates with safety and see how the concentration of drug changes over time. The third main question is to see if ELVN-002 works to shrink cancers that have HER2 genetic abnormalities, particularly non-small cell lung cancer.

Inclusion Criteria:Phase 1a Monotherapy Dose Escalation and Exploration:Pathologically documented advanced stage solid tumorProgressed following all standard treatment or not appropriate for standard treatmentHER2 mutation, HER2 amplification or HER2 positive based on local testingPhase 1b MonotherapyPathologically documented unresectable and/or metastatic non-squamous NSCLCHER2 mutation identified by tissue (fresh or archival) or ctDNA. Local testing for up to 20 patients the remainder centrally confirmed.Measurable diseaseNo known epidermal growth factor receptor (EGFR), ROS1, anaplastic lymphoma kinase (ALK), or BRAF V600E mutationProgressed 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 allowedNo limit on prior number of therapiesPhase 1a Combination with T-DXdPathologically documented advanced stage NSCLCProgressed after receiving at least 1 prior systemic therapy.HER2 mutation based on local/historical testing of tissue or circulating tumor DNANo known EGFR, ROS1, ALK, or BRAF V600E mutationNo prior T-DXdNo clinically severe pulmonary compromiseNo limit on prior number of therapiesPhase 1a Combination Breast CancerDocumented HER2 positive (Immunohistochemical [IHC] 3+ or IHC2+/in situ hybridization (ISH+) breast cancerMust have previously received trastuzumab, a taxane, and T-DXd (if available and appropriate) in the metastatic setting.No limit on prior number of therapiesNo prior T-DM1All PhasesEastern Cooperative Oncology Group performance status of 0-1Left ventricular ejection fraction ≥ 50%Platelet count ≥ 100 x 109/LHemoglobin ≥ 8.5 g/dLAbsolute neutrophil count ≥1.0 x 109/LTotal bilirubin < 1.5 times upper limit of normal range (ULN), except for patients with Gilbert's syndromeAspartate aminotransferase (AST), alanine aminotransferase (ALT) < 3 times ULN. In the setting of liver metastases < 5 times ULN.Creatinine clearance ≥ 60 mL/minuteExclusion 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 curativelyActive or chronic liver diseaseActive infection requiring systemic therapy within 14 days before the first doseBrain lesion requiring immediate local therapyLeptomeningeal diseaseUncontrolled seizuresCorrected QT interval (QTc) of >470 milliseconds (ms) females or >450 ms for males by Fridericia (QTcF)