Sacituzumab Tirumotecan Plus Third-Generation TKI With/Without Radiotherapy for EGFR-Mutant NSCLC Brain Metastases

NCT ID: NCT07343479

Last Updated: 2026-01-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-05-01
• Study Completion Date: 2029-12-20

Brief Summary

This is a prospective, open-label, multi-center, single-arm clinical trial

Detailed Description

The purpose of this study is to assess the efficacy and safety of sac-TMT combined with third-generation EGFR-TKI with/without intracranial radiotherapy in subjects with EGFR-mutated NSCLC and brain metastasis who have failed prior EGFR-TKI treatment. Eligible subjects will receive sac-TMT (4 mg/kg, twice weekly (Q2W)) + third-generation EGFR-TKI ± intracranial radiotherapy. The decision to initiate intracranial radiotherapy will be determined by the investigator based on the patient's clinical condition.

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer); EGFR Gene Mutations; Brain Metastasis

Study Design

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

Study Groups

sac-TMT plus EGFR-TKI

Sacituzumab tirumotecan combined with third-generation EGFR-TKI with or without intracranial radiotherapy

Group Type: EXPERIMENTAL

sac-TMT plus EGFR-TKI

Intervention Type: DRUG

Eligible subjects will receive sac-TMT (4 mg/kg, twice weekly (Q2W)) + third-generation EGFR-TKI ± intracranial radiotherapy. The decision to initiate intracranial radiotherapy will be determined by the investigator based on the patient's clinical condition.

Interventions

sac-TMT plus EGFR-TKI

Eligible subjects will receive sac-TMT (4 mg/kg, twice weekly (Q2W)) + third-generation EGFR-TKI ± intracranial radiotherapy. The decision to initiate intracranial radiotherapy will be determined by the investigator based on the patient's clinical condition.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 and ≤ 75 years at the time of signing the informed consent form (ICF), regardless of gender;
• Histologically or cytologically confirmed non-squamous NSCLC, and metastatic (Stage IV);
• Confirmed EGFR sensitizing mutation including exon 19 deletion (19-Del) or exon 21 point mutation (L858R);
• Subject has previously received EGFR-TKI therapy for locally advanced or metastatic disease and has experienced radiological PD;
• Subjects with new or previously diagnosed brain metastasis confirmed by contrast-enhanced cranial MRI;
• ECOG performance status scale of 0 or 1;
• Life expectancy ≥ 12 weeks;
• Adequate organ and bone marrow function;

Exclusion Criteria

• Tumor histology or cytology confirms combined small cell lung cancer (SCLC), neuroendocrine carcinoma, carcinosarcoma components, or squamous cell carcinoma;
• Known leptomeningeal metastases;
• Other malignant tumors within 3 years prior to the first dose (except for tumors cured by local treatment, such as basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, etc.);
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >470 ms, and other serious cardiovascular and cerebrovascular diseases within 6 months before study intervention;
• Uncontrolled systemic diseases as judged by the investigators;
• Clinically severe pulmonary impairment due to concurrent lung disorders, including but not limited to any underlying lung disorder (e.g., pulmonary embolism within 3 months before the first dose, severe asthma, severe chronic obstructive pulmonary disease, restrictive pulmonary disease, pleural effusion, etc.) or any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (i.e., rheumatoid arthritis, sicca syndrome, sarcoidosis, etc.), or prior pneumonectomy;
• Subjects with active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, intra-abdominal abscess, or acute gastrointestinal hemorrhage;
• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease;
• Active infection requiring systemic therapy;
• Active hepatitis B [hepatitis B surface antigen (HBsAg) positive, requiring hepatitis B virus deoxyribonucleic acid (HBV-DNA) testing; HBV-DNA ≥500 IU/mL or above the lower limit of detection, whichever is higher] or hepatitis C [hepatitis C antibody positive, and hepatitis C virus ribonucleic acid (HCV-RNA) above the lower limit of detection];
• Positive human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection;
• History of allogeneic tissue/solid organ transplant.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Zhejiang Cancer Hospital

OTHER

Sponsor Role: lead

Responsible Party

Fan Yun, MD

Director of the Department of Thoracic Oncology, Zhejiang Cancer Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yun Fan, Doctor

Role: STUDY_DIRECTOR

Zhejiang Cancer Hospital

Hui Li, Doctor

Role: STUDY_DIRECTOR

Zhejiang Cancer Hospital

Locations

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Countries

China

Central Contacts

Hui Li, Doctor

Role: CONTACT

lihui@zjcc.org.cn

+8657188122092

Facility Contacts

Li Hui, Doctor

Role: primary

lihui@zjcc.org.cn

057188122092

Other Identifiers

IRB-2025-1523（IIT）

Identifier Type: -

Identifier Source: org_study_id