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

Starting soon · Phase 1

Conditions studied: EGFR-TKI-resistant Non-small Cell Lung Cancer With Leptomeningeal Metastasis

In brief

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.

Key facts

Study ID

NCT07702305

Run by

Henan Cancer Hospital

People needed

15

Starts

2026-06-23

Expected to finish

2027-12-31

Last updated by the study team

2026-07-14

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age ≥ 18 years;
• Pathologically diagnosed as EGFR mutation-positive non-small cell lung cancer;
• Leptomeningeal metastasis confirmed by detection of tumor cells in cerebrospinal fluid cytology;
• Previously received targeted therapy against EGFR mutation and progressed;
• ECOG performance status ≤ 3;
• Neurological symptoms stable for more than 7 days (defined as no new or worsening neurological symptoms and no more than a 1-point change in ECOG score);
• If radiotherapy (including whole-brain radiotherapy, stereotactic radiotherapy, etc.) has been received, at least 7 days after completion; if other intrathecal therapy has been received, a washout period of at least 7 days;
• Absolute neutrophil count ≥ 1.5 × 10⁹/L, hemoglobin ≥ 80 g/L, platelet count ≥ 75 × 10⁹/L;
• Prothrombin time/international normalized ratio and partial thromboplastin time ≤ 1.5 × upper limit of normal;
• Total bilirubin ≤ 1.5 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (elevations of total bilirubin and transaminases caused by tumor may be relaxed to 3× and 5×, respectively), creatinine ≤ 2 × upper limit of normal; calculated creatinine clearance ≥ 50 mL/min.

You may not qualify if…

• Active infectious disease within 7 days before the start of study drug treatment;
• ECOG performance status ≥ 4;
• History of allergy to any component of the study drug;
• History of severe hypersensitivity reaction to any monoclonal antibody;
• Patients currently participating in other interventional studies;
• Previous or current severe immunodeficiency disease;
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in this study.

Full record on ClinicalTrials.gov

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