Sacituzumab Tirumotecan (Sac-TMT) Plus Bevacizumab in 3rd Generation EGFR-TKI Treated Advanced EGFR-mutant Nonsquamous NSCLC With Brain Metastasis

NCT ID: NCT07197008

Last Updated: 2025-09-29

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-01
• Study Completion Date: 2028-12-30

Brief 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. 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sacituzumab tirumotecan plus bevacizumab

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.

Group Type: EXPERIMENTAL

Sacituzumab tirumotecan (Sac-TMT) plus bevacizumab

Intervention Type: DRUG

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.

Interventions

Sacituzumab tirumotecan (Sac-TMT) plus bevacizumab

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 and ≤80 when signing the informed consent form, regardless of gender;

2. Histologically or cytologically confirmed nonsquamous NSCLC with EGFR-sensitive mutation (exon 19 deletion or exon 21 L858R mutation).

3. 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).

4. 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.

5. 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.

6. ECOG PS 0-1.

7. Estimated life expectancy of 12 weeks or more.

8. Adequate organ function.

9. 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.

10. 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.

Exclusion Criteria

1. Histologically or cytologically confirmed tumor with components of small cell lung cancer, neuroendocrine carcinoma, carcinosarcoma, or squamous cell carcinoma;

2. Patients with spinal cord compression or those assessed by the investigator as having extensive meningeal metastasis;

3. Previous whole-brain radiotherapy for brain metastases;

4. 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);

5. 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;

6. A history of bleeding tendency or coagulation disorder and/or clinically significant bleeding symptoms or risks within 4 weeks before the first dose;

7. Use of aspirin (> 325 mg/day) or treatment with dipyridamole or clopidogrel within 2 weeks before the first dose;

8. Use of full-dose oral or intravenous anticoagulants or thrombolytics within 2 weeks before the first dose;

9. Biopsy or other minor surgeries (excluding placement of vascular access devices) within 7 days before the first dose;

10. Presence of non-healing wounds or untreated fractures (excluding old fractures and other fractures that do not require treatment);

11. 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.);

12. Presence of any of the following cardiovascular and cerebrovascular diseases or risk factors:

1. 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;

2. Previous history of myocardial diseases such as myocarditis, primary cardiomyopathy, or specific cardiomyopathy;

3. 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;

4. 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;

13. Uncontrolled systemic diseases as judged by the investigator:

14. 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;

15. Documented history of severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or severe corneal diseases that may impede/delay corneal healing;

16. 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;

17. Subjects with active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, abdominal abscess, or acute gastrointestinal bleeding;

18. 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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Li-kun Chen

OTHER

Sponsor Role: lead

Responsible Party

Li-kun Chen

doctor

Responsibility Role: SPONSOR_INVESTIGATOR

Central Contacts

Likun Chen

Role: CONTACT

chenlk@sysucc.org.cn

+8613798019964

Other Identifiers

2025-FXY-287

Identifier Type: -

Identifier Source: org_study_id