Oral Paclitaxel Solution With Immunotherapy and Concurrent SBRT as Neoadjuvant Treatment for Older Adults With NSCLC

Older patients with NSCLC may have reduced organ reserve, more comorbidities, and a higher risk of toxicity from standard platinum-based chemotherapy, intensive radiotherapy, or multimodality treatment. The study is designed to explore a potentially lower-intensity neoadjuvant regimen that combines oral paclitaxel solution, immune checkpoint blockade, and precision radiotherapy. Phase I will use a conventional 3+3 dose-escalation design. Oral paclitaxel solution will be evaluated at 80, 120, and 160 mg/m² on Days 1 and 8 of each cycle, administered in divided morning and evening doses. An anti-PD-1 or anti-PD-L1 monoclonal antibody will be selected by the investigator according to standard of care and administered according to the approved prescribing information. Concurrent SBRT will be delivered at 8 Gy per fraction for 3 fractions to the primary lung tumor and selected nodal regions. The Phase I objective is to evaluate safety and identify the RP2D. Phase II will enroll additional participants at the RP2D to evaluate antitumor activity and feasibility. Participants who remain suitable for radical lung cancer surgery are intended to undergo resection after completion of neoadjuvant treatment. The study will assess pathologic response, radiographic response, surgical feasibility, event-free survival, overall survival, and changes in immune cell subsets, circulating tumor DNA, and PD-L1 expression.