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Here, we present clinical and translational results from a single-arm, prospective phase 1b\/2 investigator-initiated study (NCT03970252) evaluating neoadjuvant modified FOLFIRINOX (mFFX) plus nivolumab in patients with borderline-resectable PDAC. The co-primary endpoints of safety and pathological response rate were met, with 22 (79%) of 28 patients proceeding to surgery and no grade \u22653 immune-related adverse events. All grade 3-4 treatment-related adverse events were chemotherapy-related. By CAP scoring, 9% of patients achieved a complete pathologic response, 9% a near-complete response, and 72% a partial response. Secondary endpoints included CA 19-9 response rate, R0 resection rate, objective response rate, and disease-free survival (median 19.7 months, 95% CI: 7.3-30.8). In post-hoc analyses, median progression-free survival was 26 months (95% CI: 14.7-34.3), and median overall survival was 38 months (95% CI: 27.9-not reached). Exploratory gene expression, immunohistochemistry and spatial transcriptomics showed increased intratumoral plasma cells and CD8 T cells in treated patients versus mFFX-only controls, and lymphoid aggregates with high plasma-cell-to-B cell ratios enriched for terminally exhausted CD8 T cells with fewer progenitor exhausted CD8 T cells and central memory CD4 T cells.<\/jats:p>","DOI":"10.1038\/s41467-026-68976-2","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T21:44:27Z","timestamp":1769895867000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Neoadjuvant modified FOLFIRINOX plus nivolumab in borderline-resectable pancreatic ductal adenocarcinoma: a pilot phase 1 trial"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7142-1246","authenticated-orcid":false,"given":"Zev A.","family":"Wainberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6892-0431","authenticated-orcid":false,"given":"Jason M.","family":"Link","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alykhan","family":"Premji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3666-0513","authenticated-orcid":false,"given":"Serena","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0485-4154","authenticated-orcid":false,"given":"Michael","family":"Srienc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"McKensie","family":"Hammons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shineui E.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Tsvetkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan R.","family":"Abt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O. 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