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Non-Small Cell Lung CancerPhase 2NCT07789444

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

A Phase 2 study testing brain radiotherapy and Sacituzumab Tirumotecan (Sac-TMT) in people with Non-Small Cell Lung Cancer and Brain Metastases From Non-small Cell Lung Cancer (NSCLC), run by Xiaorong Dong.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
brain radiotherapy and Sacituzumab Tirumotecan (Sac-TMT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
No sites listed yet
Study dates
30 Aug 2026to 1 Dec 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Willing and able to provide written informed consent and comply with study follow-up.

Who cannot join

  • 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.
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  • 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).
  • History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis that required steroids, current ILD/non-infectious pneumonitis, or suspected ILD/non-infectious pneumonitis that cannot be excluded by imaging at screening.
  • Documented severe dry eye syndrome, severe meibomian gland disease, and/or blepharitis, or history of severe corneal disease that prevents/delays corneal healing.
  • Clinically severe pulmonary impairment due to concurrent lung disease, including but not limited to any underlying lung disease (e.g., severe asthma within 3 months before first dose, severe COPD, restrictive lung disease) or any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis), or prior total pneumonectomy.
  • Active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, intra-abdominal abscess, or acute gastrointestinal bleeding.
  • Active gastrointestinal disease or other conditions that significantly affect absorption, distribution, metabolism, or excretion of oral study drugs (however, this study uses IV administration; still included per protocol) - e.g., refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow capsules, or prior major bowel resection.
  • Risk of esophagotracheal fistula or esophagopleural fistula, or tumor invasion/compression of vital organs or vessels (e.g., heart, esophagus, superior vena cava) with associated symptoms (e.g., superior vena cava syndrome).
  • Prior anti-tumor therapy toxicity not recovered to ≤ grade 1 (per NCI CTCAE v5.0) or to the level specified in the eligibility criteria (except alopecia, fatigue, or other low-risk toxicities per investigator judgment).
  • Active autoimmune disease requiring systemic treatment within the past 2 years (e.g., disease-modifying agents, immunosuppressants, systemic corticosteroids >10 mg/day prednisone or equivalent). Hormone replacement therapy (e.g., thyroid hormone, insulin, or physiologic corticosteroid replacement for adrenal/pituitary insufficiency) is not considered systemic treatment. Subjects receiving systemic corticosteroids >10 mg/day prednisone or other immunosuppressants within 2 weeks before first dose are excluded.
  • Severe infection within 4 weeks before first dose (including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia), or active infection requiring systemic anti-infective therapy within 2 weeks before first dose.
  • Known active tuberculosis. Subjects with suspected active tuberculosis must be ruled out by clinical examination.
  • Active hepatitis B (HBsAg positive with HBV-DNA ≥500 IU/mL or above the lower limit of detection, whichever is higher) or active hepatitis C (HCV antibody positive with HCV-RNA above the lower limit of detection), or co-infection with HBV and HCV.
  • Positive HIV test or history of AIDS; known active syphilis infection.
  • History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
  • Major surgery within 4 weeks before first dose, or planned major surgery during the study.
  • Known hypersensitivity to the study drug or any of its components (including polysorbate-20), or history of severe hypersensitivity reactions to other biologics.
  • Receipt of non-specific immunomodulatory therapy (including but not limited to interferon, IL-2) or Chinese patent medicines with approved anti-tumor indications within 2 weeks before first dose.
  • Receipt of strong CYP3A4 inhibitors or inducers within 7 days before first dose, or need for continued use of these drugs during the study.
  • Vaccination with live vaccine within 30 days before first dose, or planned live vaccination during the study.
  • Rapid deterioration of clinical condition during the screening period (e.g., significant change in performance status).
  • Pregnancy or breastfeeding.
  • Any other condition that, in the investigator's opinion, would interfere with the evaluation of the study drug, subject safety, or interpretation of study results, or that makes the subject unsuitable for participation.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Xiaorong Dong, MD, PhD contact

027-85726375

xr.dong@gmail.com

About this study

Official title: A Phase II, Multicenter Study of Sacituzumab Tirumotecan (SKB264) Combined With Brain Radiotherapy in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer With Brain Metastasis After Progression on First-Line Third-Generation EGFR-Tyrosine Kinase Inhibitors

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.

Read more

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.

Being tested
brain radiotherapy, Sacituzumab Tirumotecan (Sac-TMT)
Keywords
Sacituzumab Tirumotecan（Sac-TMT/SKB264）、Brain Radiotherapy、EGFR-TKI Resistance、Intracranial Progression-Free Survival
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • brain radiotherapyRadiation

    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 groups in NCT07789444
Study groupRoleWhat they receive
Sacituzumab Tirumotecan（Sac-TMT/SKB264）+ Brain RadiotherapyExperimentalParticipants 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.
Receives: Radiation: brain radiotherapy; Drug: Sacituzumab Tirumotecan (Sac-TMT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. 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.

    Measured: 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.

  2. 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.

    Measured: 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.

  3. 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.

    Measured: 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.

  4. Overall Survival (OS)

    Overall survival (OS) is defined as the time from the first dose of study treatment to death from any cause.

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

  5. Incidence and Severity of Adverse Events

    Safety and tolerability assessed by the incidence, severity, and relationship of adverse events (AEs), treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) graded per NCI CTCAE v5.0.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Aug 2026
  2. Study start30 Aug 2026 (estimated)
  3. Primary completion1 Jul 2027 (estimated)
  4. Study completion1 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
53 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07789444
Sponsor's protocol ID
SKB264-SSIP-015
Status last verified
Jul 2026
First submitted
24 Aug 2026
Last updated
27 Aug 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing brain radiotherapy and Sacituzumab Tirumotecan (Sac-TMT) in people with Non-Small Cell Lung Cancer and Brain Metastases From Non-small Cell Lung Cancer (NSCLC), run by Xiaorong Dong.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Xiaorong Dong, MD, PhD (027-85726375, xr.dong@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07789444.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.

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