Clinical Research Directory

Inclusion Criteria 1. Diagnosis, Stage, and Resectability * Histologically or cytologically confirmed non-small cell lung cancer (NSCLC). * Clinical stage IB-IIIB according to the 9th edition IASLC/AJCC TNM classification. * For stage IB disease, only patients with a maximum tumor diameter of 4.0 cm (cT2aN0M0) are eligible. * The disease must be considered resectable by multidisciplinary team (MDT) assessment with curative-intent surgery planned after neoadjuvant treatment. * The primary lung lesion must be technically amenable to percutaneous biopsy and CT-guided Cryo-Thermal Ablation.. * No prior systemic or local anti-tumor therapy for the current NSCLC. 2. Age, Performance Status, and General Condition * Age 18-80 years. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Estimated life expectancy \>6 months. * Able to understand and voluntarily sign the informed consent form and willing to comply with study treatment, specimen collection, and follow-up requirements. 3. Tumor Tissue and Pulmonary Function * Willing to provide tumor tissue and blood samples required by the study protocol. * Adequate pulmonary function for the planned treatment and subsequent pulmonary resection, including: FEV1 ≥1.2 L or ≥50% of predicted value; and predicted postoperative FEV1≥30% of predicted value. 4. Adequate Organ Function Laboratory assessments performed within 7 days before the first study intervention must meet the following criteria: * Hemoglobin ≥9.0 g/dL; * absolute neutrophil count ≥1.0 × 10⁹/L; * platelet count ≥90 × 10⁹/L; * total bilirubin ≤2.0 × upper limit of normal (ULN); * alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤2.5 × ULN; * serum creatinine ≤2.0 mg/dL and creatinine clearance ≥60 mL/min; * adequate thyroid function. If thyroid-stimulating hormone (TSH) is outside the normal range, free T3 and free T4 must be within clinically acceptable limits; no clinically significant abnormality in cardiac enzyme testing; * international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5 × ULN, unless abnormalities are attributable to protocol-permitted anticoagulation. 5. Reproductive Requirements * Female participants of childbearing potential must have a negative serum or urine human chorionic gonadotropin (HCG) pregnancy test within 7 days before initiation of study treatment. * Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception from enrollment until at least 180 days after the last dose of study systemic therapy. Exclusion Criteria 1. Histological or Molecular Characteristics * Small-cell lung cancer (SCLC) or mixed histology containing a small-cell component. * Presence of protocol-defined actionable oncogenic alterations detected by tumor tissue and/or plasma-based molecular testing, including: * EGFR sensitizing or protocol-defined activating alterations, including exon 19 deletion, L858R, G719X, S768I, L861Q, or exon 20 insertion; * ALK rearrangement; * ROS1 rearrangement; * MET exon 14 skipping alteration or protocol-defined MET amplification; * KRAS G12C; * BRAF V600E; * NTRK1/2/3 fusion; * RET rearrangement; or HER2 alteration as defined in the study protocol. 2. Contraindications to Percutaneous Biopsy or Cryo-Thermal Ablation * Active clinically significant hemoptysis, defined as ≥1/2 teaspoon of fresh blood, within 2 weeks before the planned procedure. * Clinically significant bleeding tendency or coagulation disorder that cannot be adequately corrected before biopsy or ablation. * Therapeutic anticoagulant or vitamin K antagonist treatment that cannot be safely interrupted or managed during the periprocedural period according to the study protocol and institutional practice. Stable anticoagulation may be permitted when appropriate periprocedural interruption or management is considered safe by the investigator. * Active infection involving the planned biopsy or ablation site or access pathway. * Any anatomical or clinical condition considered by the investigator to make percutaneous biopsy or combined Cryo-Thermal Ablation unsafe. 3. Clinically Significant Cardiovascular or Systemic Disease * Uncontrolled hypertension. * Unstable angina, myocardial infarction within 3 months before enrollment, New York Heart Association (NYHA) class II or higher heart failure considered clinically significant by the investigator, or severe/uncontrolled arrhythmia. * Severe or uncontrolled hepatic, renal, metabolic, or other systemic disease that could interfere with study treatment or assessment. 4. Immunotherapy-Related Contraindications * Active or suspected autoimmune disease requiring systemic treatment, except for conditions permitted by the protocol, such as vitiligo, type 1 diabetes mellitus, or adequately controlled autoimmune hypothyroidism. * History of autoimmune disease requiring systemic treatment with disease-modifying agents, corticosteroids, or immunosuppressive therapy within 2 years before enrollment, except as specifically permitted by the protocol. * Requirement for chronic systemic immunosuppressive treatment. * Systemic glucocorticoid treatment within 7 days before initiation of systemic study treatment, except physiologic replacement therapy equivalent to prednisone ≤10 mg/day. * Uncontrolled peripheral neuropathy of grade ≥2 or other condition that, in the investigator's judgment, would substantially increase the risk of study treatment. * Psychiatric, cognitive, or other conditions that would prevent adequate informed consent or compliance with study procedures. 5. Active or Clinically Significant Infection * Active tuberculosis or inadequately controlled tuberculosis treated within 1 year before enrollment. * Human immunodeficiency virus (HIV) infection with clinically significant immunodeficiency or acquired immunodeficiency syndrome (AIDS), as defined by the study protocol. * Active hepatitis B infection with HBV DNA above the protocol-defined acceptable limit. * Active hepatitis C infection with detectable HCV RNA. * Other uncontrolled active infection requiring systemic therapy that, in the investigator's judgment, would interfere with study treatment. 6. Pulmonary Conditions * Interstitial lung disease, interstitial pneumonia, pneumoconiosis, drug-induced pneumonitis, or other clinically significant diffuse pulmonary disease that may increase the risk of study treatment. * Severe impairment of pulmonary function incompatible with the planned ablation, systemic therapy, or subsequent surgical resection. * Clinically uncontrolled pleural or pericardial effusion. Participants whose effusion is adequately controlled and clinically stable after drainage may be eligible according to investigator assessment and the study protocol. 7. Other Malignancies * Another malignancy diagnosed within 2 years before enrollment, except malignancies with a negligible risk of metastasis or death that have been adequately treated, such as basal cell or squamous cell carcinoma of the skin or carcinoma in situ treated with curative intent. 8. Concurrent or Recent Treatments * Participation in another interventional clinical trial or receipt of another investigational drug or investigational device within 4 weeks before the first study intervention. * Receipt of anti-cancer traditional Chinese patent medicines or systemic immunomodulatory agents, including thymosin, interferons, or interleukins, within 2 weeks before initiation of study treatment. * Receipt of a live attenuated vaccine within 30 days before initiation of study treatment. Inactivated vaccines, including inactivated influenza vaccines, are permitted. 9. Pregnancy, Lactation, and Transplantation * Pregnancy or breastfeeding. * Unwillingness to comply with protocol-specified contraceptive requirements. * Previous organ or bone marrow transplantation, or planned transplantation during the study period. 10. Other Exclusion Criteria * Known severe hypersensitivity or contraindication to toripalimab, protocol-specified chemotherapy agents, their excipients, or materials used in the ablation procedure. * Any other medical, psychological, social, or logistical condition that, in the investigator's judgment, makes the participant unsuitable for study enrollment or could interfere with treatment safety, protocol compliance, or interpretation of study results.