Esenyurt

Researchers are evaluating the safety, effectiveness, and how the body processes zipalertinib in adults with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) that has specific mutations in the Epidermal Growth Factor Receptor (EGFR) gene, including exon 20 insertions and other uncommon mutations. This Phase 2b study also explores potential drug interactions of zipalertinib with certain enzyme and transporter substrates and aims to find the best dosing plan for the medication. Participants will be enrolled into one of four main groups based on their specific EGFR mutation status and treatment history. These groups include those previously treated with exon 20 insertion agents, those untreated and unsuitable for standard chemotherapy, those with active brain metastases or leptomeningeal disease, and those with other uncommon EGFR mutations without prior systemic therapy. Additionally, separate substudies will assess drug interactions using enzyme and transporter probe cocktails and will test different doses of zipalertinib in randomized groups until treatment discontinuation. Throughout the study, participants will undergo regular assessments including imaging scans, neurological exams, and laboratory tests to monitor disease progression and treatment safety. Researchers will track response rates over up to two years and evaluate brain metastasis stability when applicable. Safety monitoring, including cardiac function and adverse effects, will be ongoing. The study requires tissue samples to confirm mutation status and participants will be followed closely to evaluate the medication's impact and tolerability.