Neoadjuvant modified FOLFIRINOX plus nivolumab in borderline-resectable pancreatic ductal adenocarcinoma: a pilot phase 1 trial

作者：Zev A. Wainberg, Jason M. Link, Alykhan Premji, Serena Zheng, Michael Srienc, McKensie Hammons, Shineui Kim, L. Li, Zeyu Liu, Olga Tsvetkova, Evan R. Abt, Lee S. Rosen, Stephen S. Kim, J.C. King, O. Joe Hines, Mark Girgis, S. Sadeghi, Olga Olevsky, D. Wong, Lisa Yonemoto, Ann Marie Siney, Kim Kelly, Christine Kivork, Chi-Hong Tseng, Caius G. Radu, David W. Dawson, Timothy R. Donahue · 发表于：Nature Communications · 年份：2026 · DOI：10.1038/s41467-026-68976-2 · 被引用次数：2 · 研究领域：Pancreatic and Hepatic Oncology Research、Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses

Chemotherapy and immune checkpoint inhibitor combinations have failed to improve survival in pancreatic ductal adenocarcinoma (PDAC), except in rare microsatellite instability-high cases; most studies focused on advanced disease. 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 ≥3 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...