{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:12:52Z","timestamp":1778649172284,"version":"3.51.4"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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 \u201cradio-immuno-chemotherapy\u201d strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\/m\u00b2 + nab-Paclitaxel 125 mg\/m\u00b2, Days 1, 8, Q3W and SBRT (33\u201350 Gy\/5 fractions) initiated in Cycle 2, or the Control Group receiving GnP alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcomes<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1817221","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:46:08Z","timestamp":1778647568000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["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)"],"prefix":"10.3389","volume":"17","author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"Division of Abdominal Tumor, 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