Toripalimab Combined With Cryoablation for First-line Oligo-progression in Driver-negative Advanced NSCLC

Inclusion criteria

• Voluntary participation and written informed consent;
• histologically or cytologically confirmed advanced metastatic (stage IV) non-small cell lung cancer;
• Patients with negative driver genes who develop oligoprogression after receiving standard first-line therapy. The oligoprogression is defined as: 1-5 metastatic lesions, and no more than 3 organs;
• Age 18-75 years old; ECOG PS: 0-1; The expected survival is more than 3 months;
• At least one measurable lesion;
• Patients were willing to provide adequate blood and tissue samples；
• Patients had adequate hematologic, renal, and liver function;
• International normalised ratio (INR) ≤1.5 and partial thromboplastin time (PTT or aPTT) ≤1.5 x ULN within 7 days prior to study treatment;
• The woman patients of childbearing age who must agree to take contraceptive methods during the research;
• The man patients who must agree to take contraceptive methods during the research and within another 6 months after it.

Exclusion criteria

• cytologically or histologically confirmed combination with small cell lung cancer component or sarcomatoid element;
• Previously received targeted therapy for advanced NSCLC (including osimertinib, erlotinib, crizotinib, etc);
• Had undergone major surgical operations or had not fully recovered from previous operations within 3 weeks before enrollment;
• Known active nervous system (CNS) metastases and/or carcinomatous meningitis;
• Spinal cord compression for which operation and/or radical radiotherapy has not been given, or no clinical evidence of stable disease for ≥4 weeks prior to enrollment after treatment for previously diagnosed spinal cord compression;
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; patients with stable symptoms after drainage can be enrolled;
• History of idiopathic pulmonary fibrosis, organized pneumonia (e.g., obliterating bronchiolitis), drug induced pneumonia, idiopathic pneumonia or evidence of active pneumonia during chest CT scanning for screening;
• Clinically uncontrolled active infection, including but not limited to acute pneumonia;
• Uncontrollable major epileptic seizure or superior vena cava syndrome;
• Previous or current co-occurrence of other malignancies (excluding controllable non-melanoma basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the breast or cervix, superficial bladder cancer, or other carcinoma in situ);
• Known hepatic diseases of clinical significance, including active viral hepatitis, alcoholic hepatitis or other hepatitis, liver cirrhosis, fatty liver, hereditary liver disease;
• Active tuberculosis (TB), receiving anti-tuberculosis therapy currently or within one year prior to screening;
• Use of systemic immunosuppressive therapy for any active autoimmune disease within two years prior to Day 1 of the 1st cycle;
• Vaccination of live-virus vaccine within 30 days after the start of planned treatment; Inactivated seasonal influenza vaccine was permitted;
• Patients has HIV-positive;
• Patients judged by the investigator to be inappropriate as a subject of this study.
• History of severe allergic, quasi-allergic, or other hypersensitive reactions to chimeric or humanized antibodies or fusion proteins;
• Known allergy to biological drugs produced from Chinese hamster ovary cells, or to citrate monohydrate, sodium citrate dihydrate, mannitol, polysorbate (components of the study drug);
• Patients who have previously received allogeneic stem cells or parenchymal organ transplants.