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.
Age ≥ 18 years, any sex.
Histologically or cytologically confirmed advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) (per AJCC 8th edition TNM staging).
Radiologically confirmed brain metastases and considered suitable for brain radiotherapy by the investigator.
Presence of EGFR-sensitizing mutations, including exon 19 deletion or exon 21 L858R point mutation.
Histological or cytological evidence of small cell lung cancer, neuroendocrine carcinoma, carcinosarcoma, or squamous cell carcinoma components.
Prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC other than third-generation EGFR-TKI (first-line EGFR-TKI combined with chemotherapy is allowed).
Prior treatment with any TROP2-targeted therapy or any drug containing a topoisomerase I inhibitor, including antibody-drug conjugates (ADCs) (including in the adjuvant/neoadjuvant setting).
Known leptomeningeal metastases, brainstem metastases, spinal cord metastases, or spinal cord compression.
Single group
brain radiotherapy
RadiationAfter 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)
DrugA 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.
Intracranial Progression-Free Survival (iPFS)
Intracranial progression-free survival (iPFS) is defined as the time from the first dose of study treatment to the first documented intracranial disease progression per RECIST 1.1 criteria as assessed by the investigator, or death from any cause, whichever occurs first.
Intracranial Objective Response Rate (iORR)
Intracranial objective response rate (iORR) is defined as the proportion of participants with a confirmed intracranial complete response (CR) or partial response (PR) per RECIST 1.1 criteria as assessed by the investigator.
Overall Response Rate (ORR)
Overall response rate (ORR) is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 criteria as assessed by the investigator.
Progression-Free Survival (PFS)
Progression-free survival (PFS) is defined as the time from the first dose of study treatment to the first documented intracranial or extracranial radiological disease progression per RECIST 1.1 criteria as assessed by the investigator, or death from any cause, whichever occurs first.
Overall Survival (OS)
Overall survival (OS) is defined as the time from the first dose of study treatment to death from any cause.
Click on the lead sponsor to view all of their trials.
Xiaorong Dong
Lead sponsor
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Sponsor institution
This trial is not recruiting at the moment. You can still explore other options:
