Spatially Fractionated Radiotherapy With Tislelizumab and Chemotherapy for Bulky Stage III NSCLC: A Phase II Trial

This is a prospective, single-arm, multicenter phase II clinical study evaluating the efficacy and safety of spatially fractionated radiotherapy (SFRT) combined with tislelizumab and platinum-based doublet chemotherapy as induction/conversion therapy for patients with potentially resectable stage III non-small cell lung cancer (NSCLC) with bulky disease (primary tumor \>5 cm). SFRT, also known as lattice radiation therapy, is a novel radiotherapy technique that creates alternating high-dose and low-dose regions within the tumor. This approach not only reduces tumor burden but also may enhance anti-tumor immune responses, potentially working synergistically with immunotherapy. Study participants will receive SFRT to the primary lung tumor (GTV 20 Gy/5 fractions, GTV-Lattice 60 Gy/5 fractions), followed by 2-4 cycles of tislelizumab (200 mg, Q3W) combined with platinum-based doublet chemotherapy. Surgery will be performed 4-6 weeks after the last cycle of neoadjuvant therapy. The first 6 enrolled patients will undergo dose-limiting toxicity (DLT) assessment within 21 days after the first dose of study drug. The primary endpoint is major pathological response (MPR) rate, defined as the proportion of patients with ≤10% viable tumor cells in the resected specimen. Secondary endpoints include 1-year event-free survival (EFS), pathological complete response (pCR) rate, objective response rate (ORR), disease control rate (DCR), R0 resection rate, 1-year overall survival (OS), time to distant metastasis (TTDM), and safety. A total of 44 patients will be enrolled across multiple centers in China. An interim analysis will be conducted after 50% of patients are enrolled.