Serplulimab combined with gemcitabine, nab-paclitaxel, and stereotactic body radiotherapy versus gemcitabine and nab-paclitaxel as first-line treatment for recurrent or metastatic pancreatic ductal adenocarcinoma: a randomized, open-label, multicenter, phase III clinical trial (WGOG-PAN 006/ICSBR-2).

内容摘要

Pancreatic ductal adenocarcinoma remains a malignancy with a dismal prognosis, characterized by a median overall survival of less than one year in the metastatic setting despite standard-of-care chemotherapy regimens like gemcitabine plus nab-paclitaxel. The PDAC tumor microenvironment is notoriously immunosuppressive, rendering single-agent immune checkpoint inhibitors largely ineffective. Stereotactic Body Radiotherapy has emerged as a potential strategy to induce immunogenic cell death and remodel the TME. Based on promising Phase II data demonstrating a 78.48% 6-month progression-free survival rate with the triplet combination of GnP, Serplulimab and SBRT, this Phase III trial aims to validate the efficacy of this "radio-immuno-chemotherapy" strategy. This prospective, randomized, open-label, multicenter Phase III study will enroll 198 patients with recurrent or metastatic PDAC who are naive to systemic therapy for advanced disease. Participants will be randomized (1:1) to the Experimental Group receiving Serplulimab (300 mg IV, Q3W) combined with Gemcitabine 1000 mg/m² + nab-Paclitaxel 125 mg/m², Days 1, 8, Q3W and SBRT (33-50 Gy/5 fractions) initiated in Cycle 2, or the Control Group receiving GnP alone. The primary endpoint is Overall Survival. Secondary endpoints include progression-free survival, Objective Response Rate, Disease Control Rate, and safety profiles assessed via NCI-CTCAE v5.0. Exploratory endpoints include cyclic multiplex tissue staining assays to evaluate immune spatial interactions. This study addresses the critical unmet need in advanced PDAC by evaluating a mechanistic synergy between cytotoxic debulking, radiation-induced immune priming, and checkpoint blockade. If successful, this regimen could establish a new standard of care.