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

NCT07702305 | Not Yet Recruiting Phase 1

• 1 other identifier: 2026-151
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

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

Keywords

Sacituzumab tirumotecan; Intrathecal injection; EGFR-TKI-resistant; NSCLC; Leptomeningeal metastasis

Outcome Measures

Primary Outcomes (2)

• Drug Safety

  Adverse events (AEs) and serious adverse events (SAEs) are recorded according to the CTCAE 5.0 criteria, with special attention to bone marrow suppression, neurotoxicity, chemical meningitis, etc.

  Assessments are performed before each dose, and monitoring continues for 2 weeks after the last dose.

• Recommended Phase 2 Dose

  Determined based on DLT incidence, adverse event grading (CTCAE 5.0), and comprehensive safety data.

  Within 21 days after the first dose (DLT observation period).

Study Arms (1)

sac-TMT

EXPERIMENTAL

Intrathecal injection of Sacituzumab tirumotecan.

Drug: Sacituzumab tirumotecan

Interventions

Sacituzumab tirumotecan DRUG

Intrathecal injection of Sacituzumab tirumotecan.

sac-TMT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Sponsors & Collaborators

• Henan Cancer Hospital: lead

MeSH Terms

Conditions

Meningeal Carcinomatosis

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: July 9, 2026
• First Posted: July 14, 2026
• Study Start: June 23, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 14, 2026

Record last verified: 2026-07