Osimertinib and Cyclosporine A to Enhance Antitumor Efficacy in NSCLC

Brief Summary

This single-site, biomarker-enriched, randomized Phase II study will evaluate osimertinib with or without cyclosporine A (CsA) in metastatic epidermal growth factor receptor (EGFR )-mutant non-small cell lung cancer (NSCLC) \[exon 19 deletion or L858R\]. All consented, baseline circulating tumor DNA (ctDNA)-positive patients receive a 3-week osimertinib run-in; those with persistent ctDNA ("shedders") are randomized 1:1 to continue osimertinib or osimertinib+CsA. Plasma is collected approximately every 3 weeks in both arms for molecular response monitoring. The investigators plan to enroll 60 patients with approximately 40 "shedders" randomized with 20 enrolled in each arm. All patients will be treated with osimertinib daily throughout the study; the combination of osimertinib+CsA will receive CsA. Imaging will be performed as per standard of care.