NVL-330, a selective HER2 tyrosine kinase inhibitor, in patients with advanced or metastatic HER2-altered non-small cell lung cancer: The phase 1 HEROEX-1 study
Recommended Citation
Le X, Piotrowska Z, Spira AI, Baik CS, Baggstrom MQ, Falchook GS, Neal JW, Gadgeel SM, Lopes G, Johnson ML, Riess JW, Nguyen D, Morelli L, Sandino D, Margossian S, Upadhyay V, Santini F. NVL-330, a selective HER2 tyrosine kinase inhibitor, in patients with advanced or metastatic HER2-altered non-small cell lung cancer: The phase 1 HEROEX-1 study. 2025; (16_suppl).
Document Type
Conference Proceeding
Publication Date
5-28-2025
Abstract
Background: Oncogenic mutations and gene amplifications in the HER2 receptor tyrosine kinase are detected in approximately 2-4% and 1-5% of non-small cell lung cancers (NSCLC) in the US, respectively. Exon 20 insertion mutations (exon20ins) are the predominant HER2 mutations in NSCLC, and ∼50% of patients with HER2-mutant metastatic NSCLC develop brain metastases. The antibody drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) has received FDA accelerated approval for HER2-mutant NSCLC, but no tyrosine kinase inhibitors (TKIs) are currently approved for this indication. NVL-330 is a novel, brain-penetrant, HER2-selective investigational TKI, designed to address the medical need of targeting HER2-mutant tumors, and treating brain metastases, while minimizing treatment related adverse events due to off-target inhibition of wild-type EGFR. Methods: HEROEX-1 (NCT06521554) is a first-inhuman, Phase 1a/1b trial. The Phase 1a dose escalation portion employs a Bayesian optimal interval design with a 3+3 run-in, followed by a Phase 1b dose expansion. The study population includes adult patients with advanced or metastatic NSCLC with a HER2 oncogenic mutation (Phase 1a/1b) or amplification (Phase 1a only) determined by local testing. Eligible patients must have received at least one prior systemic therapy including platinum-based chemotherapy with or without immunotherapy, or are unsuitable candidates for available therapies. Prior HER2-directed antibodies and HER2-directed ADCs are allowed. Prior HER2 TKIs are allowed in Phase 1a only. Patients will receive NVL-330 by oral administration once or twice daily. The primary objectives are to evaluate safety and tolerability, determine the recommended Phase 2 dose, and, if applicable, the maximum tolerated dose of NVL-330. Additional objectives include assessment of preliminary activity and characterization of the pharmacokinetic and pharmacodynamic profiles of NVL-330. Analyses will be performed to evaluate tumor and blood-based biomarkers of response and other relevant biomarkers. The study is open to accrual.
Issue
16_suppl
