Safety and Efficacy of Intrathecal Sacituzumab Tirumotecan for Leptomeningeal Metastasis in EGFR-TKI-Resistant Non-Small Cell Lung Cancer

This study is a Phase I, single-arm, single-center, dose-escalation clinical trial designed to investigate the safety and efficacy of intrathecal injection of sacituzumab tirumotecan (sac-TMT) in patients with EGFR mutation-positive non-small cell lung cancer and leptomeningeal metastasis who have progressed after prior EGFR-TKI therapy, and to determine the optimal dose (RP2D). The study employs an "accelerated titration" combined with a "3+3" dose-escalation design, with a starting dose of 0.05 mg/kg, sequentially escalating to 0.5 mg/kg. The drug is administered via intrathecal injection through an Ommaya reservoir once every 14 days, along with concomitant intrathecal injection of dexamethasone 5 mg to prevent chemical meningitis. The primary endpoints are safety (incidence, severity, and grading of adverse events and serious adverse events) and the recommended dose (RP2D). Secondary endpoints include intracranial objective response rate, time to treatment failure, progression-free survival, and overall survival. The study plans to enroll 8-15 subjects. Efficacy assessment is based on evaluation of neurological symptoms, cerebrospinal fluid cytology, and neuroimaging changes. Special attention is given to adverse events of special interest, including neurotoxicity and bone marrow suppression. This study aims to provide a new treatment strategy for patients with leptomeningeal metastasis after EGFR-TKI resistance and to generate pioneering data for the intrathecal administration of ADC drugs.