Non-Small Cell Lung Cancer
Conditions
Interventions
Test group:Trastuzumab Rezetecan + Furmonertinib
Sponsors
The second affiliated hospital of Zhejiang University school of medicine
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Provide fully informed and voluntarily signed written informed consent, and be willing and able to comply with study procedures. 2. Age >= 18 years. 3. Histologically or cytologically confirmed unresectable, locally advanced or metastatic (stage IIIB, IIIC, or IV) non-small cell lung cancer (NSCLC) that is not eligible for definitive concurrent chemoradiotherapy, with staging according to the 9th edition of the IASLC/AJCC TNM classification for lung cancer. 4. Presence of an EGFR-sensitive mutation confirmed prior to first-line EGFR-TKI therapy. 5. Radiologically confirmed disease progression after first-line EGFR-TKI therapy (for patients previously treated with first- or second-generation TKIs, T790M-negative status is required). 6. HER-2 overexpression (IHC 3+ or 2+) confirmed by central assessment after disease progression on first-line therapy. 7. At least one measurable lesion according to RECIST v1.1 criteria. 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 9. Life expectancy > 12 weeks. 10. Adequate bone marrow reserve and organ function. 11. Female patients of childbearing potential must agree to use effective contraception from the screening period until 4 weeks after discontinuation of the study drug. 12. Male subjects must agree to practice abstinence (refrain from heterosexual intercourse) or use contraceptive measures, and agree not to donate sperm. 13. Patients with asymptomatic brain metastases are permitted for enrollment.
Exclusion criteria
Exclusion criteria: 1. T790M mutation-positive patients. 2. Prior treatment with HER-2-targeted therapy. 3. Currently suffering from other malignancies, or having had other invasive malignancies within the past 5 years. 4. Prior systemic anti-tumor therapy other than EGFR-TKIs for advanced NSCLC. 5. Currently receiving anti-angiogenic therapy, traditional Chinese medicines with anti-tumor indications, extensive-field radiotherapy, palliative local radiotherapy, or major surgery; or currently participating in other drug clinical trials and using the corresponding investigational drugs, etc. 6. Use of strong CYP3A4 inducers or strong CYP1A2 inhibitors within 2 weeks prior to the start of study treatment. 7. Insufficient recovery from toxicity and/or complications due to any interventional therapy prior to the start of treatment. 8. Presence of clinically significant active infections, including but not limited to active tuberculosis, or human immunodeficiency virus (HIV) infection (HIV-1/2 antibody positive). 9. Active hepatitis B or active hepatitis C. 10. Recent occurrence of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack. 11. Known presence of tumor thrombus, deep vein thrombosis, or hypertension uncontrolled despite medication. 12. Abnormal mean corrected QT interval (QTcF) at rest, or presence of any significant cardiac arrhythmia. 13. Presence of leptomeningeal metastases, spinal cord compression, or active brain metastases prior to the start of study treatment. 14. Presence of active gastrointestinal diseases or other conditions that significantly affect the absorption, distribution, metabolism, or excretion of the oral study drug. 15. Judged by the investigator to be non-compliant with this clinical study or unable to comply with study restrictions and requirements. 16. Subjects with known or suspected interstitial pneumonia; or other moderate-to-severe pulmonary diseases occurring within 3 months prior to the first dose that may interfere with the monitoring or management of drug-related pulmonary toxicity and significantly affect respiratory function, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia / bronchiolitis obliterans, pulmonary embolism, severe asthma, severe COPD, severe obstructive / restrictive ventilatory dysfunction, etc., as well as any autoimmune, connective tissue, or inflammatory diseases involving the lungs, such as rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc., or a history of total pneumonectomy. Subjects who experienced = Grade 3 interstitial pneumonia during prior treatment with immune checkpoint inhibitors are not permitted to be enrolled in this study. 17. Pregnant or lactating women. 18. Receipt of systemic immunosuppressive therapy (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, etc.) within 14 days prior to the first study drug administration. Inhaled or topical corticosteroids and physiologic replacement doses of corticosteroids are permitted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression?free survival (PFS);Overall survival (OS);Duration of response (DoR);Disease control rate (DCR); | — |
Countries
China
Contacts
Public ContactYang Xia
The second affiliated hospital of Zhejiang University school of medicine
Outcome results
None listed