Advanced non-small cell lung cancer
Conditions
Interventions
Experimental group:Ruconatuzumab combined with tagolizumab
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. The age at signing the informed consent form should be between 18 and 75 years old (inclusive), with no gender restrictions; 2. Confirmed by histological or cytological examination, and being locally advanced (stage IIIB/III C) or metastatic (stage IV) NSCLC that is not suitable for radical surgery and/or radical radiotherapy (regardless of whether concurrent or sequential chemotherapy is received) [according to the International Union Against Cancer and the American Joint Committee on Cancer (AJCC) 9th edition of lung cancer TNM staging]; 3. There should be no known driver gene alterations such as EGFR, ALK, ROS1, etc. For squamous NSCLC patients with a smoking history, if the previous EGFR and ALK gene status is unknown, no corresponding tests need to be conducted before enrollment in this study and it is regarded as negative; 4. For locally advanced or metastatic diseases that have received PD-1/L1 inhibitor and platinum-based double-drug chemotherapy (combined or sequential, with no specific order for sequential) treatment or experienced disease progression after treatment (the previous immunotherapy PFS is >= 3 months); 5. The ECOG performance status score of the US Eastern Cooperative Oncology Group (ECOG) was 0 or 1 within 7 days before the first administration; 6. The expected survival period is >= 3 months; 7. According to RECIST 1.1, at least one measurable lesion must be present. Patients with only skin lesions or bone lesions are not eligible for inclusion. Brain lesions are not considered as target lesions; 8. Gastrointestinal and bone radiation therapy for palliative purposes (including cranial radiotherapy for symptomatic brain metastases) is allowed, but the radiotherapy must be completed at least 2 weeks before the first administration and the radiotherapy-related toxicity must recover to less than or equal to grade 1 (CTCAE 5.0, except for hair loss); 9. Adequate organ and bone marrow functions (no blood transfusion, recombinant human thrombopoietin or colony-stimulating factor treatment within 2 weeks before the first administration), defined as follows: a) Blood routine: Neutrophil count (NEUT#) >= 1.5×10^9/L; Platelets (PLT) >= 100×10^9/L; Hemoglobin >= 90 g/L; b) Liver function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 30 g/L; Total bilirubin (TBIL) = 50 ml/min (calculated using the standard Cockcroft-Gault formula); d) Coagulation function: International normalized ratio (INR), activated partial thromboplastin time (APTT), and prothrombin time (PT) <= 1.5×ULN; 10. For female subjects with reproductive capacity and male subjects whose partners have reproductive potential, they must agree to take effective medical contraceptive measures from the date of signing the informed consent form to 6 months after the last administration (see Appendix 2); The subjects voluntarily join this study, sign the informed consent form, and can comply with the visit and related procedures as stipulated in the protocol.
Exclusion criteria
Exclusion criteria: 1. Tumor histology or cytology confirmed the presence of combined small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma components; 2. Oligometastasis: Judged comprehensively by the investigators based on the specific progression site, number, and suitability for local treatment of the patient; 3. Previous treatment with any of the following (including in the context of adjuvant or neoadjuvant therapy): a) Targeted therapy against TROP2; b) Any drug treatment containing targeted topoisomerase I, including antibody-conjugated drug (ADC) therapy; 4. Subjects known to have meningeal metastasis, brainstem metastasis, spinal cord metastasis and/or compression, active or untreated brain metastases. For subjects with brain metastases who have received local treatment previously, if they are clinically stable at least 4 weeks before the first administration of the study treatment and did not need to use glucocorticoids or anticonvulsants at least 14 days before the first administration, they can participate in the study; for subjects with brain metastases identified for the first time during screening, if they have received local treatment (such as radiotherapy), there must be imaging evidence showing that the brain metastasis lesion is at least 4 weeks from the first imaging diagnosis of brain metastasis and stable before enrollment; 5. Within 3 years before administration of the study drug, had other malignant tumors (excluding those cured by local treatment, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, cervical carcinoma in situ, etc.); 6. Subjects who need to use strong inhibitors or inducers of cytochrome P450 3A4 enzyme (CYP3A4) (in this study, strong inhibitors or inducers of CYP3A4 are not allowed); 7. Subjects who received > 10 mg/day prednisone for systemic corticosteroid treatment or other immunosuppressive drugs within 2 weeks before the first administration of the study drug. Subjects who need to use bronchodilators, inhaled or topical steroids or local steroid injections as preventive medication for hypersensitivity reactions (such as before CT examination, etc.) can be allowed to enroll; 8. Subjects who received live vaccines 4 weeks before the first administration of the study drug; 9. Imaging during the screening period showed tumor invasion or compression of important surrounding organs and blood vessels (or there is a risk of esophageal-tracheal fistula or esophageal pleural fistula;. 10. Subjects with a history of immunodeficiency or positive HIV antibody test or active autoimmune diseases requiring systemic treatment in the past 2 years; 11. Subjects with any of the following cardiovascular or cerebrovascular diseases or risk factors: a) Within 6 months before administration, myocardial infarction, unstable angina pectoris, acute or persistent myocardial ischemia, grade 3 or 4 heart failure [according to the New York Heart Association (NYHA) classification], symptomatic or poorly controlled severe arrhythmia, cerebrovascular accident, transient cerebral ischemia attack, other serious cardiovascular diseases; b) Previous history of myocarditis, primary cardiomyopathy, specific cardiomyopathy, etc.; c) Any deep vein thrombosis within 3 months before administration (if treated with low molecular weight heparin or similar efficacy drugs and stable for >= 2 weeks, can be allowed to enroll), peripheral arterial thromboembolic events, pulmonary embolism or other serious thromboemboli
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Adverse event;Progression-free survival ;Duration of relief;Disease control rate;Overall survival ; | — |
Countries
China
Contacts
Public ContactPanwen Tian
West China Hospital of Sichuan University
Outcome results
None listed