A Multicenter, Open-Label, Single-Arm Phase I/II Study of Oral Paclitaxel Solution Combined With an Immune Checkpoint Inhibitor and Concurrent Stereotactic Body Radiotherapy as Neoadjuvant Treatment in Older Patients With Resectable Stage IIA-IIIB Non-Small Cell Lung Cancer
his multicenter, open-label, single-arm phase I/II trial will evaluate the safety, tolerability, and preliminary efficacy of oral paclitaxel solution combined with an immune checkpoint inhibitor and concurrent stereotactic body radiotherapy (SBRT) as neoadjuvant therapy in patients aged 70 years or older with resectable stage IIA-IIIB non-small cell lung cancer (NSCLC) without sensitizing EGFR, ALK, or ROS1 alterations. In Phase I, a 3+3 dose-escalation design will evaluate oral paclitaxel at 80, 120, and 160 mg/m² administered orally on Days 1 and 8 of each cycle, divided into morning and evening doses, in combination with an investigator-selected anti-PD-1 or anti-PD-L1 monoclonal antibody and SBRT at 8 Gy in 3 fractions. Phase II will expand enrollment at the recommended Phase II dose (RP2D). The principal efficacy outcome is pathologic complete response after surgery. Other outcomes include major pathologic response, radiographic response, event-free survival, overall survival, surgical resection and R0 resection rates, and exploratory biomarker changes.
• Age 70 years or older, regardless of sex.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed non-small cell lung cancer, clinical stage IIA-IIIB according to the 8th edition of the AJCC staging system.
• No evidence of distant metastasis and considered suitable for radical lung cancer surgery.
• The primary lung lesion is suitable for stereotactic body radiotherapy.
• No sensitizing driver alterations in EGFR, ALK, ROS1, or other tested actionable genes.
• Adequate major organ function, including all of the following:
• Absolute neutrophil count at least 1.5 × 10\^9/L, platelet count at least 100 × 10\^9/L, and hemoglobin at least 9 g/dL.
• Total bilirubin no more than 1.5 × the upper limit of normal; alanine aminotransferase and aspartate aminotransferase no more than 2.5 × the upper limit of normal.
• Serum creatinine no more than 1.5 × the upper limit of normal or creatinine clearance at least 60 mL/min.
• Urine protein less than 1+; if urine protein is 1+, 24-hour urine protein must be less than 500 mg.
• Blood glucose within the normal range or stable glycemic control in participants with diabetes.
• Baseline forced expiratory volume in 1 second (FEV1) at least 2 L; if FEV1 is less than 2 L, the predicted postoperative FEV1 must be greater than 800 mL as assessed by a thoracic surgeon.
• No myocardial infarction within the previous year, no unstable angina, no symptomatic severe arrhythmia, and no cardiac insufficiency.
• The participant has been fully informed and voluntarily provides written informed consent.