{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T22:52:45Z","timestamp":1781477565863,"version":"3.54.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Pancreatic cancer remains a leading cause of death with poor prognosis. Current standard chemotherapies offer limited survival benefits, and no standard treatment exists for patients failing two lines of therapy. Preclinical evidence suggests that targeting MNK and VEGFR pathways can remodel the immunosuppressive tumor microenvironment and enhance immunotherapy efficacy. This study evaluates the safety and efficacy of JDB153 (an MNK\/VEGFR inhibitor) combined with serplulimab (an anti-PD-L1 antibody) in refractory advanced pancreatic cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a prospective, open-label, single-center, phase Ib\/II clinical trial (NCT07175389). It will enroll patients with advanced pancreatic adenocarcinoma who have progressed after standard therapies. The study follows a Simon\u2019s two-stage design. The initial phase will enroll 10 patients to test safety and preliminary efficacy. Patients will receive oral JDB153 and intravenous serplulimab. If at least one patient responds, the study will expand to a total of 32 patients. The primary endpoints are safety and ORR. Secondary endpoints include DFS, OS, and PFS. Safety will be graded using NCI-CTCAE version 5.0. Comprehensive biomarker analyses (PD-L1 expression, spatial immune profiling, next-generation sequencing, et al.) are integrated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Patients with advanced pancreatic cancer need effective options that are less toxic than chemotherapy. Immunotherapy alone often fails in this disease due to the immunosuppressive microenvironment. By combining MNK\/VEGFR inhibition with PD-1 blockade, this study investigates a promising strategy to overcome immune resistance and establish a novel treatment paradigm for advanced pancreatic adenocarcinoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1805590","type":"journal-article","created":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T22:10:25Z","timestamp":1781475025000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and efficacy of the MNK\/VEGFR inhibitor JDB153 combined with the anti-PD-1 antibody serplulimab in patients with advanced pancreatic cancer refractory to standard treatment: a single-arm, phase Ib\/II study protocol"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaorui","family":"Zhu","sequence":"first","affiliation":[{"name":"Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wei","sequence":"additional","affiliation":[{"name":"Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Cao","sequence":"additional","affiliation":[{"name":"Division of Abdominal Tumor, Department of Medical Oncology, Cancer Center, Laboratory of Abdominal Tumor Immunology and Microenvironment, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanji","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2848","DOI":"10.1038\/onc.2012.306","article-title":"Gemcitabine triggers a pro-survival response in pancreatic cancer cells through activation of the MNK2\/eIF4E pathway","volume":"32","author":"Adesso","year":"2013","journal-title":"Oncogene"},{"key":"B2","doi-asserted-by":"publisher","first-page":"152985","DOI":"10.1016\/j.prp.2020.152985","article-title":"Frequency of mismatch repair deficiency in pancreatic ductal adenocarcinoma","volume":"216","author":"Ahmad-Nielsen","year":"2020","journal-title":"Pathol. 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