Patients with stage III non-resectable NSCLC (discussed by the MDT panel) without EGFR/ALK/ROS1/RET mutations
Conditions
Interventions
Single Arm:Ivosimanab (AK112) 20mg/kg Q3W combined with platinum-based doublet chemotherapy (squamous cell carcinoma: cisplatin/carboplatin + paclitaxel/nab-paclitaxel
non-squamous cell carcinoma: cisplatin/carboplatin + pemetrexed), for 3-4 cycles
followed by surgery or radical chemoradiotherapy based on MDT assessment, then maintenance therapy with Ivosimanab 20mg/kg Q3W for 16 cycles
Sponsors
Shanghai Chest Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age 18 to 75 years, no gender restriction; 2. Pathologically or cytologically confirmed, unresectable stage III NSCLC after MDT assessment (according to AJCC 9th edition staging, for patients with T1-4N2-3M0, chest enhanced CT and/or PET/CT examination suggests single-station N2 short axis > 3 cm, multi-station N2 short axis > 2 cm, or N3 metastasis); 3. No prior local treatment (surgery or radiotherapy) for NSCLC, nor any prior systemic anti-tumor therapy, including cytotoxic therapy, targeted therapy (including tyrosine kinase inhibitors or monoclonal antibodies), cellular therapy, immunotherapy, traditional Chinese medicine, or any other research drug therapy; 4. Sufficient tumor tissue (non-cytological specimens) available for molecular marker analysis (NGS and IHC); 5. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); 6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; 7. Pulmonary function at least FEV1 > 1.2 L and FEV1% > 40% within 3 months; possibility of radical surgical resection and systematic lymph node dissection, under the condition of ensuring surgical margins and comprehensively considering the patient's general condition; 8. Adequate major organ function: (1) Hematopoietic function, defined as absolute neutrophil count >= 1.5 × 10^9/L, platelet count >= 100 × 10^9/L, hemoglobin >= 9.0 g/dL; (2) Liver function, defined as total bilirubin = 28 g/L; (3) Renal function: 1) Serum creatinine = 45 mL/min - For patients planned to receive cisplatin: CrCl >= 60 mL/min - For patients planned to receive carboplatin: CrCl >= 45 mL/min * CrCl (mL/min) = {(140 - age) × body weight (kg) × F} / (SCr (mg/dL) × 72), where F = 1 for males and F = 0.85 for females; SCr = serum creatinine; 2) Urine protein 6 months; 10. For patients planned to receive cisplatin therapy: no hearing impairment; 11. Women of childbearing potential must have a serum pregnancy test within 3 days before the first dose of the study drug, with a negative result. Female subjects and male subjects whose partners are women of childbearing potential must agree to use highly effective contraceptive methods during the study period and within 180 days after the last dose of the study drug; 12. Have fully understood the study and voluntarily signed the informed consent form (ICF).
Exclusion criteria
Exclusion criteria: 1. T4 tumors invading the aorta, esophagus, heart, and/or other organs or tissues; or T4 tumors with ipsilateral intrapulmonary metastasis in different lobes; 2. Fusion or multi-station lymph nodes encasing or invading the aorta, pulmonary artery, trachea, esophagus, heart, etc., and MDT evaluation deems radical resection impossible; 3. According to the 9th edition staging, NSCLC patients with clinical stage IIB T1N2a, despite the short-axis diameter of single-station N2 lymph nodes exceeding 3 cm; 4. Subjects with mixed small cell lung cancer, neuroendocrine carcinoma, or sarcoma components; 5. Subjects harboring driver gene mutations for which targeted therapy is available (e.g., EGFR, ALK, ROS1, RET); (1) For non-squamous cell carcinoma subjects (including NSCLC with unclear pathological type), EGFR/ALK/ROS1/RET test results based on tumor tissue must be provided. If the gene status is unknown, testing for EGFR/ALK/ROS1/RET must be performed before enrollment; (2) For squamous non-small cell lung cancer subjects, if the EGFR/ALK/ROS1/RET gene status is unknown, testing at screening is not required; 6. Any prior anti-tumor therapy for current lung cancer (e.g., radiation therapy, targeted therapy, ablation, or other systemic or local anti-tumor treatment); 7. Subjects who have previously received thoracic radiotherapy; 8. History of (non-infectious) pneumonia/interstitial lung disease requiring steroid therapy, or current pneumonia/interstitial lung disease requiring steroid therapy; 9. Known history of active tuberculosis; 10. Previous history of severe allergic reaction to other monoclonal antibodies; 11. Any unstable systemic disease, including active infection, uncontrolled hypertension (systolic blood pressure >=140 mmHg or diastolic blood pressure >=90 mmHg despite optimal medical therapy), unstable angina pectoris, angina pectoris attacks within the last 3 months, liver disease, kidney disease, or metabolic disease requiring medication; 12. Cardiac function and disease meeting one of the following conditions: (1) Arrhythmias considered clinically significant by the investigator, with obvious abnormalities and unsuitable for enrollment in this trial, including but not limited to complete left bundle branch block, second-degree atrioventricular block; (2) 12-lead electrocardiogram (ECG) measurement showing QTc interval >=450 ms in males and >=470 ms in females; (3) New York Heart Association (NYHA) classification >= grade 3 cardiac insufficiency or echocardiographic examination: left ventricular ejection fraction (LVEF) = grade 3) within 4 weeks before the first medication, including but not limited to infectious complicat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Surgical Conversion Rate;Major Pathological Response (MPR);Pathological Complete Response (pCR);R0 Resection Rate;Lymph Node Downstaging Rate;Event-Free Survival (EFS);1-year/2-year Event-Free Survival Rate;Overall Survival (OS);Adverse Events (AE); | — |
Countries
China
Contacts
Public ContactYao Feng
Shanghai Chest Hospital
Outcome results
None listed