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

NCT07197008 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025-FXY-287
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

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

Keywords

brain metastases; EGFR mutated; Sacituzumab tirumotecan

Outcome Measures

Primary Outcomes (1)

• intracranial objective response rate

  proportion of patients with complete or partial response of intracranial lesions

  6-months

Secondary Outcomes (5)

• intracranial progression-free survival

  12-months

• systemic objective response rate

  6-months

• progression-free survival

  12-months

• overall survival

  36-months

• adverse events

  12-months

Study Arms (1)

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.

Drug: Sacituzumab tirumotecan (Sac-TMT) plus bevacizumab

Interventions

Sacituzumab tirumotecan (Sac-TMT) plus bevacizumab 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.

Sacituzumab tirumotecan plus bevacizumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Li-kun Chen: lead

MeSH Terms

Conditions

Lung Neoplasms; Brain Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Likun Chen

CONTACT

+8613798019964; chenlk@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: doctor

Model Details: 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.

Study Record Dates

• First Submitted: September 20, 2025
• First Posted: September 29, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share