Serplulimab combined with gemcitabine, nab-paclitaxel, and stereotactic body radiotherapy as first-line treatment for metastatic pancreatic adenocarcinoma: a multicentre, single-arm, phase II trial

Abstract Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a highly aggressive cancer associated with extremely poor outcomes. We postulated that a combination of immunotherapy, chemotherapy, and stereotactic body radiation therapy (ICSBR) could offer improved efficacy against mPDAC. In this multicentre, single-arm, phase II study, we evaluated the combination of serplulimab, gemcitabine plus nab-paclitaxel, and radiotherapy as first-line treatment for mPDAC patients. The primary endpoint was the investigator-assessed 6-month progression-free survival (PFS) rate. Forty-seven patients were enrolled and received at least one dose of treatment. The primary endpoint was met, with a 6-month PFS rate of 78.7% (95% confidence interval CI, 67.9%–91.3%). The objective response rate was 74.5% (95% CI, 59.7%–86.1%) by local investigator review, and the median PFS and overall survival durations were 8.6 months (95% CI, 7.6–12.0 months) and 15.5 months (95% CI, 10.8 months to not reached), respectively. The combination treatment was well tolerated, and no treatment-related deaths or unexpected safety signals were observed. Analysis of programmed death-ligand 1 (PD-L1) expression, within-tumour genomic features, dynamic circulating tumour DNA, and the tumour microenvironment suggested that spatial cell interactions and an integrated immune microenvironment spatial score can be applied to predict treatment response. Overall, the tested ICSBR combination demonstrated significant antitumour activity as first-line treatment for mPDAC, and a further phase III randomized trial is necessary to verify this finding. Chinese Clinical Trial Registry: ChiCTR2300073237.