Radiotherapy combined with serplulimab, and chemotherapy as first-line treatment for metastatic pancreatic adenocarcinoma: a multicenter, single-arm, phase II trial

PURPOSE: The prognosis for metastatic pancreatic ductal adenocarcinoma (mPDAC) remains dismal. In this multicenter, single-arm, phase II study, we evaluated the combination of serplulimab, gemcitabine plus nab-paclitaxel, and radiotherapy (ICSBR regimen) as first-line treatment for mPDAC patients (ChiCTR2300073237). METHODS: Patients with mPDAC were enrolled in the first-line setting. The treatment regimen consisted of serplulimab and gemcitabine plus nab-paclitaxel administered in 21-day cycles, combined with stereotactic body radiotherapy directed at the primary or metastatic sites during cycle 2. Additionally, comprehensive biomarker analysis was conducted. The primary endpoint was the 6-month progression-free survival (PFS) rate, with a predefined target of 60%. RESULT: Forty-six patients received at least one dose of treatment. The 6-month PFS rate was 78.3% (95% CI, 67.2%-91.1%). The median PFS and overall survival (OS) were 8.5 months (95% CI, 7.3-12.0 months) and 14.0 months (95% CI, 12.0 months-not reached), respectively. The objective response rate was 73.9% (95% CI, 58.9%-85.7%). The combination treatment was well tolerated, and no treatment-related deaths or unexpected safety signals were observed. Notably, patients with baseline ctDNA negativity achieved a better survival. Moreover, tumor microenvironment (TME) analysis revealed that baseline fibroblast activation protein-positive cancer-associated fibroblast and T-cell proportions in tumor tissue correlated with clinical outcomes, with distinct spatial distribution and interaction tendencies observed among patients with different responses. CONCLUSION: Overall, the ICSBR regimen demonstrated a promising survival benefit as first-line treatment for mPDAC. Furthermore, ctDNA status and TME analysis highlighted potential markers for guiding precision treatment.