Phase 2b Study of Zipalertinib for Advanced or Metastatic Non-Small Cell Lung Cancer With EGFR Exon 20 Insertions or Other Uncommon EGFR Mutations

What this Trial Is About

Researchers are evaluating zipalertinib, an oral drug, for safety, effectiveness, and how it behaves in the body pharmacokinetics in adults with locally advanced or metastatic non-small cell lung cancer NSCLC that has specific mutations in the epidermal growth factor receptor EGFR, including exon 20 insertions and other uncommon mutations. This Phase 2b trial also studies how zipalertinib interacts with other drugs affecting liver enzymes and transporters and aims to find the best dose for treatment. Participants join one of four main groups based on their treatment history and mutation type those previously treated for exon 20 insertion mutations, those who are untreated but not candidates for standard chemotherapy, those with active brain metastases or leptomeningeal disease, and those with other uncommon EGFR mutations without prior systemic therapy. Two additional substudies focus on drug interactions using enzyme and transporter probe cocktails, and dose optimization with participants randomly assigned to two dosing arms. Zipalertinib is taken orally twice daily continuously until disease progression or other reasons to stop. During the study, participants undergo regular evaluations including scans to measure tumor response, brain imaging if applicable, laboratory tests, heart function monitoring, and assessments of side effects. Researchers track how long participants respond to treatment, disease control, survival, and changes in heart electrical activity. Safety and drug concentration in blood are closely monitored. Participants may remain in the study for up to approximately two years to assess these outcomes.

A Study of Zipalertinib in Patients With Advanced Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions or Other Uncommon Mutation.