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

NCT07343479 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: IRB-2025-1523（IIT）
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Keywords

NSCLC with brain metastasis

Outcome Measures

Primary Outcomes (1)

• 6-month PFS rate

  6-month PFS rate as assessed by the investigators according to RECIST v1.1.

  6 months post treatment initiation date (maximum follow-up of 36 months)

Secondary Outcomes (4)

• Overall ORR and DCR

  From initiation of treatment to disease progression or death from any cause, whichever occurs first (maximum follow-up of 36 months)

• DOR

  From first disease response until tumor progression (maximum follow-up of 36 months).

• OS

  From treatment initiation to death due to any cause or last day of contact, whichever occurred first (maximum follow-up of 36 months)

• Safety endpoints

  From first dose of study treatment until 30 days after the last dose, assessed up to 36 months.

Study Arms (1)

sac-TMT plus EGFR-TKI

EXPERIMENTAL

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

Drug: sac-TMT plus EGFR-TKI

Interventions

sac-TMT plus EGFR-TKI 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.

sac-TMT plus EGFR-TKI

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead
• Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; 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

Study Officials

• Yun Fan, Doctor

  Zhejiang Cancer Hospital

  STUDY DIRECTOR

• Hui Li, Doctor

  Zhejiang Cancer Hospital

  STUDY DIRECTOR

Central Study Contacts

Hui Li, Doctor

CONTACT

+8657188122092; lihui@zjcc.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: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Department of Thoracic Oncology, Zhejiang Cancer Hospital

Study Record Dates

• First Submitted: December 13, 2025
• First Posted: January 15, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): June 20, 2027
• Study Completion (Estimated): December 20, 2029
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)