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

A Clinical Study of Sac-TMT for Injection Combined With Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) ± Radiotherapy in Subjects With EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer and Brain Metastasis Who Have Failed Prior EGFR-TKI Treatment

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

Study Overview

• Status: Not yet recruiting
• Conditions: Brain Metastasis; NSCLC (Advanced Non-small Cell Lung Cancer); EGFR Gene Mutations
• Intervention / Treatment: Drug: sac-TMT plus EGFR-TKI

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.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hui Li, Doctor; Phone Number: +8657188122092; Email: lihui@zjcc.org.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
      • Contact: Li Hui, Doctor; Phone Number: 057188122092; Email: lihui@zjcc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sac-TMT plus EGFR-TKI; Sacituzumab tirumotecan combined with third-generation EGFR-TKI with or without intracranial radiotherapy	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall ORR and DCR	Overall ORR and DCR as assessed by the investigators according to RECIST v1.1	From initiation of treatment to disease progression or death from any cause, whichever occurs first (maximum follow-up of 36 months)
DOR	DOR as assessed by the investigators according to RECIST v1.1	From first disease response until tumor progression (maximum follow-up of 36 months).
OS	Time from treatment initiation to date of death due to any cause or last day of contact.	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	Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [based on the latest version of the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI)]	From first dose of study treatment until 30 days after the last dose, assessed up to 36 months.

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital
• Collaborators: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
• Investigators: Study Director: Yun Fan, Doctor, Zhejiang Cancer Hospital; Study Director: Hui Li, Doctor, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): June 20, 2027
• Study Completion (Estimated): December 20, 2029

Study Registration Dates

• First Submitted: December 13, 2025
• First Submitted That Met QC Criteria: January 6, 2026
• First Posted (Actual): January 15, 2026

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC with brain metastasis
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Nervous System Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms
• Other Study ID Numbers: IRB-2025-1523（IIT）

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No