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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• brain radiotherapy — RADIATION
  After 1-2 cycles of SKB264 alone, participants undergo brain radiotherapy (stereotactic radiosurgery or whole-brain radiotherapy, as determined by the investigator).
• Sacituzumab Tirumotecan (Sac-TMT) — DRUG
  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.

Study Details

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.

Key Dates

First listed

Aug 27, 2026

Start date

Aug 30, 2026

Status verified

Jul 2026

Primary completion

Jul 1, 2027

Completion

Dec 1, 2028

Study Design

Enrollment

53 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

PREVENTION

Arms

• Experimental: Sacituzumab Tirumotecan（Sac-TMT/SKB264）+ Brain Radiotherapy
  Participants receive Sacituzumab Tirumotecan (Sac-TMT/SKB264) 5 mg/kg intravenously on Day 1 of each 14-day cycle. After 1-2 cycles of SKB264 alone, participants undergo brain radiotherapy (stereotactic radiosurgery or whole-brain radiotherapy, as determined by the investigator). SKB264 is paused during radiotherapy and resumed upon completion. Treatment continues until disease progression, unacceptable toxicity, or other protocol-defined discontinuation criteria are met.

Primary Outcome Measure

Intracranial Progression-Free Survival (iPFS) [ Time Frame: From date of first study treatment until the first documented intracranial progression or death from any cause, whichever comes first, assessed up to approximately 12 months. ]

Central Contacts

• Xiaorong Dong, MD, PhD
  027-85726375
  [email protected]

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