Neoadjuvant Therapy for Stage II-IIIB NSCLC
Conditions
Interventions
Neoadjuvant Treatment Group with Sacituzumab Govitecan in Combination with Tislelizumab:Patients will receive neoadjuvant treatment with lurbinectedin (4 mg/kg, every 2 weeks for 6 cycles, administere
Sponsors
Shanghai Chest Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18-75 years, male or female, at the time of signing the informed consent form. 2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 within 7 days prior to dosing. 3. Histologically or cytologically confirmed Non-Small Cell Lung Cancer (NSCLC). 4. No known actionable driver gene mutations for targeted therapy (e.g., EGFR, ALK, ROS1, RET, etc.): (1) For subjects with non-squamous cell carcinoma (including NSCLC with unspecified histology), tumor tissue-based test results for EGFR/ALK/ROS1/RET must be provided. If the mutation status is unknown, testing for EGFR/ALK/ROS1/RET, etc., must be performed prior to enrollment. (2) For subjects with squamous cell NSCLC, testing for EGFR/ALK/ROS1/RET, etc., is not mandatory during screening if the mutation status is unknown. 5. No prior local treatment (surgery or radiotherapy) or any prior systemic anti-tumor therapy for NSCLC, including cytotoxic chemotherapy, targeted therapy (including tyrosine kinase inhibitors or monoclonal antibodies), cell therapy, immunotherapy, traditional Chinese medicine therapy, or any other investigational drug therapy. 6. Assessed by a Multidisciplinary Team (MDT) as having resectable Stage II, IIIA, or IIIB (T3N2M0) NSCLC (according to UICC/AJCC 9th edition TNM staging), with at least one measurable lesion (per RECIST 1.1 criteria). 7. Patients who agree to undergo curative-intent surgery. 8. Deemed surgically resectable by the surgeon's assessment with no surgical contraindications; lung function meeting at least FEV1 > 1.2L and FEV1% > 40% within 3 months. 9. Adequate organ and bone marrow function (no transfusion, recombinant human thrombopoietin, or colony-stimulating factor treatment within 2 weeks prior to the first dose), defined as follows: (1) Hematology: Absolute neutrophil count (ANC) >= 1.5 × 10^9/L; Platelets (PLT) >= 100 × 10^9/L; Hemoglobin >= 9 g/dL. (2) Liver Function: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) = 60 mL/min (Cockcroft-Gault formula, see Appendix). (4) Coagulation: International Normalized Ratio (INR), Activated Partial Thromboplastin Time (APTT), and Prothrombin Time (PT) = 50% as measured by echocardiogram (ECHO) or multigated acquisition (MUGA) scan. 10. For female subjects of childbearing potential and male subjects with partners of childbearing potential, agreement to use effective medical contraception from the time of signing the informed consent form until 6 months after the last dose. 11. Subjects voluntarily agree to participate in this study, sign the informed consent form, and are able to comply with the protocol-specified visits and related procedures.
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will be excluded from this study: 1. T4 tumors invading the aorta, esophagus, heart, and/or other organs or tissues; or T4 tumors with ipsilateral metastasis to a different lobe of the lung. 2. Confluent or multi-station lymphadenopathy encasing or invading the aorta, pulmonary arteries, trachea, esophagus, heart, etc., which, upon Multidisciplinary Team (MDT) assessment, is deemed not amenable to radical resection. 3. Tumor histology or cytology confirming mixed small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma components. 4. Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. 5. Prior treatment targeting TROP2 and/or treatment with topoisomerase I inhibitors. 6. Requirement for strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) within 2 weeks prior to the first dose or during the study period (use of strong CYP3A4 inhibitors or inducers is prohibited in this study; see Appendix 6 for a representative list). All subjects must avoid concomitant use of any known CYP3A4-inducing drugs, herbal supplements, and/or intake of such foods as much as possible. 7. History of other malignancies within the past 5 years, except for cured carcinoma in situ of the cervix, basal cell carcinoma, or squamous cell carcinoma of the skin. 8. Known history of allergy to the investigational drugs or their components in this protocol; history of immunodeficiency; or history of organ transplantation. 9. History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment; current ILD or non-infectious pneumonitis; or suspected ILD or non-infectious pneumonitis that cannot be ruled out by imaging at screening. Clinically severe pulmonary impairment due to concurrent pulmonary diseases, including but not limited to: any underlying pulmonary disease (e.g., pulmonary embolism within 3 months prior to dosing, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.); any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.); or prior pneumonectomy. 10. Active autoimmune disease that has required systemic treatment in the past 2 years (hormone replacement therapy is not considered systemic treatment, e.g., type I diabetes, hypothyroidism requiring only thyroid hormone replacement, adrenal or pituitary insufficiency requiring only physiologic corticosteroid replacement therapy). 11. Active infection requiring systemic therapy within 2 weeks prior to the first dose. 12. Active hepatitis B [HBsAg positive, HBV-DNA testing required; HBV-DNA>=500 IU/mL or above the lower limit of detection, whichever is higher] or hepatitis C (HCV antibody positive and HCV-RNA above the lower limit of detection). *Note: Subjects who are HBsAg positive must receive anti-hepatitis B virus therapy during the study treatment period.* 13. Positive human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection. 14. Any concurrent illness that, in the investigator's judgment, poses a serious risk to patient safety or compromises the patient's ability to complete the study, including but not limited to uncontrolled hypertens
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological Complete Response (pCR) Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Major Pathological Response (MPR) Rate;R0 Resection Rate;Objective Response Rate(ORR);Event-Free Survival(EFS);Overall Survival(OS);Safety and tolerability: including incidence and severity of adverse events, drug-relatedness, dose modification/discontinuation, vital signs and laboratory parameter changes, perioperative complications, etc.; | — |
Countries
China
Contacts
Public ContactYao Feng
Shanghai Chest Hospital
Outcome results
None listed