Microwave Ablation Plus Tislelizumab and Docetaxel in Advanced NSCLC After First-Line Immunotherapy Failure

Microwave Ablation in Combination With Tislelizumab and Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer After Progression Following First-Line Immunotherapy Plus Chemotherapy: A Prospective, Single-Arm, Phase II Study

The purpose of this clinical trial is to evaluate progression-free survival (PFS) of microwave ablation in combination with tislelizumab and docetaxel in patients with advanced non-small cell lung cancer (NSCLC) who have progressed following first-line immunotherapy combined with chemotherapy.

Participants with advanced NSCLC who experienced disease progression after first-line immunotherapy plus chemotherapy will receive the following treatments:

1. Tislelizumab: 200 mg administered intravenously every 3 weeks (Q3W)
2. Docetaxel: 75 mg/m² administered intravenously every 3 weeks (Q3W) for 4-6 cycles
3. Microwave ablation, administered per protocol

Inclusion Criteria:

• Patients with cytologically or histologically confirmed non-small cell lung cancer (NSCLC), classified as stage IIIB, IIIC, or IV (AJCC 9th edition) and not eligible for curative treatment.
• Male or female patients aged ≥18 years who have provided written informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, with an expected survival of more than 6 months, and deemed suitable for microwave ablation by the investigator.
• Patients must have previously received first-line treatment with tislelizumab in combination with chemotherapy and have documented disease progression based on imaging assessments prior to enrollment. Disease progression must occur ≥6 months after initiation of first-line tislelizumab plus chemotherapy, with or without concomitant anti-angiogenic therapy.
• Adequate organ and bone marrow function, defined as follows:

Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L Platelet count ≥100 × 10⁹/L Hemoglobin ≥90 g/L White blood cell count ≥3.0 × 10⁹/L

Hepatic function:

Total bilirubin <1.5 × the upper limit of normal (ULN) Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), and alkaline phosphatase (ALP) ≤2.5 × ULN In patients with liver metastases: AST and ALT ≤5.0 × ULN In patients with liver and/or bone metastases: ALP ≤5.0 × ULN

Renal function:

Serum creatinine ≤1.5 × ULN Urine protein <2+ on urinalysis; if baseline urine protein is ≥2+, a 24-hour urine protein ≤1.0 g is required

Coagulation function:

International normalized ratio (INR) ≤1.5 Activated partial thromboplastin time (aPTT) ≤1.5 × ULN

• Cardiac function defined as left ventricular ejection fraction (LVEF) ≥50%.
• Ability to communicate effectively with the investigator and to comply with study-related visits, treatment, laboratory tests, and other study requirements.

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded from the study:

• Diagnosis of small cell lung cancer (SCLC), including mixed small cell and non-small cell lung cancer.
• Presence of symptomatic brain metastases at the start of treatment.
• Concurrent participation in another interventional clinical trial for cancer treatment.
• History of tracheoesophageal fistula, gastrointestinal perforation, gastrointestinal fistula, or intra-abdominal abscess within 6 months prior to treatment initiation.
• Presence of severe cardiovascular or cerebrovascular disease, including but not limited to:

Cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction, or significant vascular disease (including but not limited to aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to randomization; Unstable angina; Heart failure classified as New York Heart Association (NYHA) class ≥ II; Mean resting corrected QT interval (QTc) >470 ms; Any clinically significant resting electrocardiogram (ECG) rhythm, conduction, or morphological abnormalities, such as complete left bundle branch block, third-degree atrioventricular (AV) block, second-degree AV block, or PR interval >250 ms; Any factors that increase the risk of QTc prolongation or arrhythmic events, including heart failure, electrolyte abnormalities (serum/plasma potassium < LLN; magnesium < LLN; calcium < LLN), congenital long QT syndrome, family history of long QT syndrome, unexplained sudden death of a first-degree relative before the age of 40, or concomitant use of medications known to prolong the QT interval and induce torsades de pointes.

• Major surgical procedures performed within 4 weeks prior to enrollment or planned during the study period.
• Bleeding tendency, high risk of bleeding, or coagulation disorders, including thrombotic events within 6 months prior to randomization and/or history of hemoptysis within 3 months prior to randomization (defined as ≥2.5 mL per episode).
• Presence of unhealed wounds, active gastrointestinal ulcers, or fractures (excluding healed historical fractures).
• Known or suspected hypersensitivity to tislelizumab and/or any of its excipients.
• Pregnant or breastfeeding women.
• Women of childbearing potential or male participants who are unwilling to use effective contraception during the study and for 6 months after the last dose of study treatment.
• Any other condition that, in the opinion of the investigator, would render the participant unsuitable for enrollment in this study.