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

NCT07789444 | Not Yet Recruiting Phase 2

• 1 other identifier: SKB264-SSIP-015
• Study Type: interventional
• Target: 53
• Locations: 0 countries
• Sites: N/A

Brief 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

Keywords

Sacituzumab Tirumotecan（Sac-TMT/SKB264）、Brain Radiotherapy、EGFR-TKI Resistance、Intracranial Progression-Free Survival

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

Secondary Outcomes (5)

• Intracranial Objective Response Rate (iORR)

  From date of first study treatment until disease progression or start of new anti-tumor therapy, assessed every 8 weeks up to approximately 12 months.

• Overall Response Rate (ORR)

  From date of first study treatment until disease progression or start of new anti-tumor therapy, assessed every 8 weeks up to approximately 12 months.

• Progression-Free Survival (PFS)

  From date of first study treatment until the first documented progression or death from any cause, whichever comes first, assessed up to approximately 12 months.

• Overall Survival (OS)

  From date of first study treatment until death from any cause, assessed up to approximately 24 months.

• Incidence and Severity of Adverse Events

  From signing of informed consent through 30 days after the last dose of study treatment.

Study Arms (1)

Sacituzumab Tirumotecan（Sac-TMT/SKB264）+ Brain Radiotherapy

EXPERIMENTAL

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.

Radiation: brain radiotherapy; Drug: Sacituzumab Tirumotecan (Sac-TMT)

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/SKB264）+ Brain Radiotherapy

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.

Sacituzumab Tirumotecan（Sac-TMT/SKB264）+ Brain Radiotherapy

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, 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.
• Prior treatment with a third-generation EGFR-TKI as first-line therapy with documented intracranial progression, regardless of extracranial progression status.
• Any number of brain metastases is allowed; symptomatic brain metastases are permitted.
• At least one measurable intracranial target lesion per RECIST 1.1 that has not been previously irradiated or surgically treated; lesions ≥5 mm in diameter are acceptable as target lesions.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 3 months.
• Adequate organ and bone marrow function (without transfusion, thrombopoietin, or colony-stimulating factor support within 2 weeks before the first dose), defined as:
• Hematology: Absolute neutrophil count ≥1.5×10⁹/L; platelets ≥100×10⁹/L; hemoglobin ≥100 g/L.
• Hepatic: AST, ALT, and ALP ≤2.5× upper limit of normal (ULN); total bilirubin ≤1.5×ULN; albumin ≥30 g/L. For subjects with baseline liver metastases, ALT and AST ≤5×ULN and total bilirubin ≤3×ULN are allowed.
• Renal: Serum creatinine ≤1.5×ULN or calculated creatinine clearance ≥50 mL/min (Cockcroft-Gault formula).
• Coagulation: INR, APTT, and PT ≤1.5×ULN.
• Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use effective medical contraception from signing of informed consent through 6 months after the last dose.

You may not qualify if:

• 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.
• Prior radiotherapy to the brain.
• Other malignancy within 3 years before the first dose, except for curatively treated tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• Presence of any of the following cardiovascular or cerebrovascular diseases or risk factors:
• Myocardial infarction, unstable angina, acute or persistent myocardial ischemia, New York Heart Association (NYHA) Class 3 or 4 heart failure, symptomatic or uncontrolled severe arrhythmia, cerebrovascular accident, transient ischemic attack, or other severe cardiovascular/cerebrovascular events within 6 months before first dose.
• History of myocarditis, primary cardiomyopathy, or specific cardiomyopathy.
• Any deep vein thrombosis (unless stable on low-molecular-weight heparin or equivalent therapy for ≥2 weeks), peripheral arterial thromboembolic event, pulmonary embolism, or other severe thromboembolic event within 3 months before first dose.
• Aortic aneurysm, aortic dissection, or other major vascular disease that may be life-threatening or requires surgery within 6 months before first dose.
• Uncontrolled systemic diseases per investigator judgment:
• Poorly controlled diabetes (fasting blood glucose ≥10 mmol/L on two consecutive measurements).
• Poorly controlled hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg).
• Clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring repeated drainage (\>1 time/week).

Sponsors & Collaborators

• Xiaorong Dong: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Xiaorong Dong, MD, PhD

CONTACT

027-85726375; xr.dong@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief of the Department of Thoracic Oncology, Cancer Center

Model Details: This is a prospective, multicenter, single-arm, phase II interventional study. Eligible patients with EGFR-mutant advanced non-small cell lung cancer and brain metastases who have progressed on first-line third-generation EGFR-TKI will receive sacituzumab tirumotecan (an anti-TROP2 ADC) at 5 mg/kg intravenously on Day 1 of each 14-day cycle, combined with brain radiotherapy (SRS or WBRT) in a sequential manner. To mitigate the risk of radiation necrosis, the ADC is withheld during the radiotherapy period.

Study Record Dates

• First Submitted: August 24, 2026
• First Posted: August 27, 2026
• Study Start: August 30, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: August 27, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share