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Sacituzumab Tirumotecan（Sac-TMT） and Brain Radotherapy for EGFR+ NSCLC With Brain Mets

NCT07789444 · Status: NOT_YET_RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 53

Last updated 2026-08-27

No results posted yet for this study

Summary

his study is a Phase II, multicenter clinical trial evaluating the combination of an antibody-drug conjugate (ADC) called Sacituzumab Tirumotecan (SKB264) and brain radiotherapy for patients with advanced non-small cell lung cancer (NSCLC) that has spread to the brain. All participants have EGFR gene mutations and have experienced disease progression in the brain after prior treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI).

The study aims to assess how well this combination therapy controls brain tumor growth and its safety profile. Approximately 53 participants will be enrolled. The treatment involves SKB264 administered intravenously at a dose of 5 mg/kg every two weeks. Participants will receive one to two cycles of SKB264 alone, followed by brain radiotherapy (either stereotactic radiosurgery or whole-brain radiotherapy). SKB264 will be temporarily paused during radiotherapy and resumed afterward.

The study is conducted in two phases: a safety run-in phase with 5 participants to evaluate initial safety using a Bayesian monitoring model, followed by an expansion phase with 48 additional participants. The primary endpoint is intracranial progression-free survival (iPFS) as assessed by investigators using RECIST 1.1 criteria. Secondary endpoints include intracranial objective response rate (iORR), overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and safety. Exploratory endpoints include functional MRI assessments of brain function and cognitive changes, quality of life evaluations using the EORTC QLQ-C30 questionnaire, and biomarker analyses.

The study is expected to run from March 2026 to March 2028, with each participant followed for approximately 12 months. This research is sponsored by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Conditions

  • Non-Small Cell Lung Cancer
  • Brain Metastases From Non-small Cell Lung Cancer (NSCLC)
  • EGFR Mutation Positive Advanced Non-Small Cell Lung Cancer

Interventions

RADIATION

brain radiotherapy

After 1-2 cycles of SKB264 alone, participants undergo brain radiotherapy (stereotactic radiosurgery or whole-brain radiotherapy, as determined by the investigator).

DRUG

Sacituzumab Tirumotecan (Sac-TMT)

A novel anti-TROP2 ADC with a proprietary hydrolyzable linker and a topoisomerase I inhibitor payload (KL610023), achieving a high drug-to-antibody ratio of \~7.4. This intervention is specifically applied in the post-third-generation EGFR-TKI resistance setting for NSCLC patients with active brain metastases. It is administered as a fixed dose of 5 mg/kg IV on Day 1 of each 14-day cycle. Crucially, to distinguish this regimen from standard ADC monotherapy, the drug is deliberately paused and withheld during the entire course of concurrent brain radiotherapy (SRS/WBRT) to minimize the risk of radiation necrosis, making this a sequential chemoradiotherapy model rather than a concurrent one. Resumption occurs only after radiotherapy completion.

Sponsors & Collaborators

  • Xiaorong Dong

    lead OTHER

Study Design

Allocation
NA
Purpose
PREVENTION
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-08-30
Primary Completion
2027-07-01
Completion
2028-12-01

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07789444 on ClinicalTrials.gov