Lung CancerPhase 2NCT07197008
Sacituzumab Tirumotecan (Sac-TMT) Plus Bevacizumab in 3rd Generation EGFR-TKI Treated Advanced EGFR-mutant Nonsquamous NSCLC With Brain Metastasis
A Phase 2 study testing Sacituzumab tirumotecan (Sac-TMT) plus bevacizumab in people with Lung Cancer, run by Li-kun Chen.
Trial summary
This is a prospective, single-center, phase 2 clinical study to explore the efficacy and safety of Sac-TMT in combination with bevacizumab for patients with EGFR-mutated nonsquamous NSCLC with brain metastases. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Sacituzumab tirumotecan (Sac-TMT) plus bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2025to 30 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 and ≤80 when signing the informed consent form, regardless of gender;
- Histologically or cytologically confirmed nonsquamous NSCLC with EGFR-sensitive mutation (exon 19 deletion or exon 21 L858R mutation).
- Progression on or after 3rd-generation EGFR-TKI (change to the third-generation EGFR-TKIs after receiving 1st or 2nd generations of TKI, or to use the third-generation TKI in the first line are all allowed).
- Brain parenchymal metastases confirmed by cranial MRI, including asymptomatic BM or those with symptoms controlled after local treatment and/or dehydration therapy, should maintain a clinically stable state (no longer requiring glucocorticoids or anticonvulsants) for at least 2 weeks before the first dose.
- According to mRECIST 1.1, the subject must have at least one accurately measurable intracranial target lesion that has not been previously treated with local therapies such as radiation therapy or surgery. Brain metastatic lesions with a diameter of ≥ 5 mm are permitted to be designated as target lesions.
- ECOG PS 0-1.
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- Estimated life expectancy of 12 weeks or more.
- Adequate organ function.
- Female subjects of childbearing potential and male subjects whose partners are of childbearing potential must agree to use effective medical contraceptive measures from the time of signing the informed consent form until 6 months after the last dose.
- The subject voluntarily participates in this study, signs the informed consent form, and is able to comply with the study visits and related procedures as specified in the protocol.
Who cannot join
- Histologically or cytologically confirmed tumor with components of small cell lung cancer, neuroendocrine carcinoma, carcinosarcoma, or squamous cell carcinoma;
- Patients with spinal cord compression or those assessed by the investigator as having extensive meningeal metastasis;
- Previous whole-brain radiotherapy for brain metastases;
- Subjects who have previously received chemotherapy, TROP2-targeted therapy, or any drug therapy containing topoisomerase I inhibitors, including antibody-drug conjugate (ADC) therapy (including in the context of adjuvant or neoadjuvant therapy);
- Tumor invading or surrounding important surrounding organs and blood vessels (such as the heart, esophagus, superior vena cava, etc.), or with obvious necrosis, cavitation, or at risk of developing esophagotracheal fistula or esophagopleural fistula;
- A history of bleeding tendency or coagulation disorder and/or clinically significant bleeding symptoms or risks within 4 weeks before the first dose;
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- Use of aspirin (> 325 mg/day) or treatment with dipyridamole or clopidogrel within 2 weeks before the first dose;
- Use of full-dose oral or intravenous anticoagulants or thrombolytics within 2 weeks before the first dose;
- Biopsy or other minor surgeries (excluding placement of vascular access devices) within 7 days before the first dose;
- Presence of non-healing wounds or untreated fractures (excluding old fractures and other fractures that do not require treatment);
- History of other malignant tumors within 3 years before the first dose (except tumors cured by local treatment, such as cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in situ, etc.);
- Presence of any of the following cardiovascular and cerebrovascular diseases or risk factors:
- Myocardial infarction, unstable angina pectoris, acute or persistent myocardial ischemia, grade 3 or 4 heart failure (according to the New York Heart Association (NYHA) classification), symptomatic or poorly controlled severe arrhythmia, cerebrovascular accident, transient ischemic attack, or other severe cardiovascular and cerebrovascular diseases within 6 months before the first dose;
- Previous history of myocardial diseases such as myocarditis, primary cardiomyopathy, or specific cardiomyopathy;
- Any deep vein thrombosis within 3 months before the first dose (subjects with stable condition after treatment with low-molecular-weight heparin or drugs with similar effects for ≥ 2 weeks are permitted to enroll), peripheral arterial thromboembolic events, pulmonary embolism, or other severe thromboembolic events;
- Presence of major vascular diseases that may be life-threatening or require surgery within 6 months before the first dose, such as aortic aneurysm or aortic dissecting aneurysm;
- Uncontrolled systemic diseases as judged by the investigator:
- History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonia requiring steroid treatment, current ILD or non-infectious pneumonia, or suspected ILD or non-infectious pneumonia at screening that cannot be excluded by imaging examinations;
- Documented history of severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or severe corneal diseases that may impede/delay corneal healing;
- Clinically severe lung damage caused by concurrent pulmonary diseases, including but not limited to any underlying lung diseases (such as severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease within 3 months before the first dose) or any autoimmune, connective tissue, or inflammatory diseases that may involve the lungs (i.e., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), or previous pneumonectomy;
- Subjects with active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, abdominal abscess, or acute gastrointestinal bleeding;
- Proteinuria, evidenced by protein > 1.0 gram in urine test strip or 24-hour urine collection. All patients with protein ≥ 2+ in baseline urine test strip analysis must undergo 24-hour urine collection, and the protein in 24 hours must be proven to be ≤ 1 g;
- Toxicity from previous anti-tumor treatment has not recovered to ≤ grade 1 (assessed based on NCI CTCAE v5.0) or the level specified in the inclusion/exclusion criteria
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Sacituzumab Tirumotecan (Sac-TMT) Plus Bevacizumab in 3rd Generation EGFR-TKI Treated Advanced EGFR-mutant Nonsquamous NSCLC With Brain Metastasis: a Single-arm, Phase II Study（TOP BRAIN）
This is a prospective, single-center, phase 2 clinical study to explore the efficacy and safety of Sac-TMT in combination with bevacizumab for patients with EGFR-mutated nonsquamous NSCLC with brain metastases. The study will enroll 50 EGFR-sensitive mutation(19del/21L858R) nonsquamous NSCLC patients who progressed on or after 3rd generation EGFR-TKI with brain metastases.
- Conditions
- Lung Cancer
- Being tested
- Sacituzumab tirumotecan (Sac-TMT) plus bevacizumab
- Keywords
- brain metastases, EGFR mutated, Sacituzumab tirumotecan
- Medical subject headings
- Lung Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacituzumab tirumotecan (Sac-TMT) plus bevacizumabDrug
Eligible patients will receive Sacituzumab tirumotecan at a dose of 4 mg/kg in combination with bevacizumab 5mg/kg by intravenous infusion on day 1 and day 15 of each 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Sacituzumab tirumotecan plus bevacizumab | Experimental | Eligible patients will receive Sacituzumab tirumotecan at a dose of 4 mg/kg in combination with bevacizumab 5mg/kg by intravenous infusion on day 1 and day 15 of each 28-day cycle. All enrolled participants will continue to receive the study treatment until disease progression or unacceptable toxicity or patient requests to discontinue the treatment, whichever occurs first. Tumor evaluation for intracranial and extracranial lesions was independently assessed by investigators. Imaging assessments will be conducted every 6 weeks (±1 week) for the first 48 weeks, and thereafter every 8 weeks (±1 week) until disease progression, initiation of a new antitumor treatment, withdrawal of consent, loss to follow-up, death, or the end of the study, whichever occurs first. Receives: Drug: Sacituzumab tirumotecan (Sac-TMT) plus bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
intracranial objective response rate
proportion of patients with complete or partial response of intracranial lesions
Measured: 6-months
Secondary outcomes (5)
intracranial progression-free survival
time from enrollment to intracranial disease progression or death.
Measured: 12-months
systemic objective response rate
proportion of patients with complete or partial response of overall lesions
Measured: 6-months
progression-free survival
time from enrollment to systemic disease progression [intracranial or extracranial or both] or death
Measured: 12-months
overall survival
time from enrollment to death from any cause
Measured: 36-months
adverse events
the incidence rate of adverse events according to CTCAE 5.0
Measured: 12-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2025
- Study start1 Oct 2025 (estimated)
- Primary completion30 Dec 2027 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Eligible patients will receive SKB264 at a dose of 4 mg/kg in combination with bevacizumab 5mg/kg by intravenous infusion on day 1 and day 15 of each 28-day cycle. All enrolled participants will continue to receive the study treatment until disease progression or unacceptable toxicity or patient requests to discontinue the treatment, whichever occurs first.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Li-kun Chen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Li-kun Chen, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07197008
- Sponsor's protocol ID
- 2025-FXY-287
- Status last verified
- Sep 2025
- First submitted
- 20 Sep 2025
- Last updated
- 29 Sep 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sacituzumab Tirumotecan (Sac-TMT) Plus Bevacizumab in 3rd Generation EGFR-TKI Treated Advanced EGFR-mutant Nonsquamous NSCLC With Brain Metastasis: a Single-arm, Phase II Study（TOP BRAIN）
- ClinicalTrials.gov ID
- NCT07197008
- Acronym / sponsor ID
- 2025-FXY-287
- Conditions
- Lung Cancer
- Keywords
- brain metastases, EGFR mutated, Sacituzumab tirumotecan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Li-kun ChenUniversity, hospital or other
- Study start
- 1 Oct 2025 (estimated)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 29 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, single-center, phase 2 clinical study to explore the efficacy and safety of Sac-TMT in combination with bevacizumab for patients with EGFR-mutated nonsquamous NSCLC with brain metastases. The study will enroll 50 EGFR-sensitive mutation(19del/21L858R) nonsquamous NSCLC patients who progressed on or after 3rd generation EGFR-TKI with brain metastases.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Eligible patients will receive SKB264 at a dose of 4 mg/kg in combination with bevacizumab 5mg/kg by intravenous infusion on day 1 and day 15 of each 28-day cycle. All enrolled participants will continue to receive the study treatment until disease progression or unacceptable toxicity or patient requests to discontinue the treatment, whichever occurs first.
| Arm | Type | Receives |
|---|---|---|
| Sacituzumab tirumotecan plus bevacizumab | Experimental | Drug: Sacituzumab tirumotecan (Sac-TMT) plus bevacizumabEligible patients will receive Sacituzumab tirumotecan at a dose of 4 mg/kg in combination with bevacizumab 5mg/kg by intravenous infusion on day 1 and day 15 of each 28-day cycle. All enrolled participants will continue to receive the study treatment until disease progression or unacceptable toxicity or patient requests to discontinue the treatment, whichever occurs first. Tumor evaluation for intracranial and extracranial lesions was independently assessed by investigators. Imaging assessments will be conducted every 6 weeks (±1 week) for the first 48 weeks, and thereafter every 8 weeks (±1 week) until disease progression, initiation of a new antitumor treatment, withdrawal of consent, loss to follow-up, death, or the end of the study, whichever occurs first. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥ 18 and ≤80 when signing the informed consent form, regardless of gender;
- Histologically or cytologically confirmed nonsquamous NSCLC with EGFR-sensitive mutation (exon 19 deletion or exon 21 L858R mutation).
- Progression on or after 3rd-generation EGFR-TKI (change to the third-generation EGFR-TKIs after receiving 1st or 2nd generations of TKI, or to use the third-generation TKI in the first line are all allowed).
- Brain parenchymal metastases confirmed by cranial MRI, including asymptomatic BM or those with symptoms controlled after local treatment and/or dehydration therapy, should maintain a clinically stable state (no longer requiring glucocorticoids or anticonvulsants) for at least 2 weeks before the first dose.
- According to mRECIST 1.1, the subject must have at least one accurately measurable intracranial target lesion that has not been previously treated with local therapies such as radiation therapy or surgery. Brain metastatic lesions with a diameter of ≥ 5 mm are permitted to be designated as target lesions.
Key exclusion criteria (23 listed)
- Histologically or cytologically confirmed tumor with components of small cell lung cancer, neuroendocrine carcinoma, carcinosarcoma, or squamous cell carcinoma;
- Patients with spinal cord compression or those assessed by the investigator as having extensive meningeal metastasis;
- Previous whole-brain radiotherapy for brain metastases;
- Subjects who have previously received chemotherapy, TROP2-targeted therapy, or any drug therapy containing topoisomerase I inhibitors, including antibody-drug conjugate (ADC) therapy (including in the context of adjuvant or neoadjuvant therapy);
- Tumor invading or surrounding important surrounding organs and blood vessels (such as the heart, esophagus, superior vena cava, etc.), or with obvious necrosis, cavitation, or at risk of developing esophagotracheal fistula or esophagopleural fistula;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sacituzumab tirumotecan (Sac-TMT) plus bevacizumabEligible patients will receive Sacituzumab tirumotecan at a dose of 4 mg/kg in combination with bevacizumab 5mg/kg by intravenous infusion on day 1 and day 15 of each 28-day cycle. | Drug | Sacituzumab tirumotecan plus bevacizumab |
Primary outcome
intracranial objective response rate
Time frame: 6-months
proportion of patients with complete or partial response of intracranial lesions
5 secondary outcomes
intracranial progression-free survival
Time frame: 12-months
systemic objective response rate
Time frame: 6-months
progression-free survival
Time frame: 12-months
overall survival
Time frame: 36-months
adverse events
Time frame: 12-months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sacituzumab tirumotecan (Sac-TMT) plus bevacizumab in people with Lung Cancer, run by Li-kun Chen.
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 10 inclusion and 23 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 29 Sep 2025. 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 Likun Chen (+8613798019964, chenlk@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
intracranial objective response rate (time frame: 6-months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Sep 2025.