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This phase 1b\/2 study aimed to evaluate SHR-1701 (an anti-PD-L1\/TGF-\u03b2RII fusion protein) plus AG in this population (NCT04624217). In phase 1b part, the recommended dose of SHR-1701 was identified as 30\u2009mg\/kg every 3 weeks, when combined with AG. In phase 2 part, the primary endpoint was objective response rate (ORR). As of Mar 31, 2023, 56 patients were enrolled. Median follow-up was 10.3 months (range, 0.2\u201324.7). ORR was 32.1% (95% CI, 20.3\u201346.0). Median progressive-free survival (PFS) was 5.6 months (95% CI, 4.3\u20136.6), and median overall survival (OS) was 10.3 months (95% CI, 8.8\u201312.3). Treatment-related adverse events of grade \u22653 were reported in 27 (48.2%) patients, with the most common being decreased neutrophil count. Patients with PD-L1 TPS\u2009\u2265\u20091% showed a higher ORR (66.7% vs. 25.0%), as well as extended median PFS (6.3 vs. 5.3 months) and median OS (18.8 vs. 9.9 months). Additionally, reduction of CA19-9 by at least 80% during treatment and pSMAD2\/3 staining intensity of 1+ at baseline were potential monitoring tools and predictive biomarkers for better clinical outcomes, respectively. Tumor-specific T-cell infiltration and pancreatic cancer tumor subtypes were associated with anti-tumor response. The interactions within tumor microenvironment were involved disease progression. Overall, first-line SHR-1701 plus AG showed promising anti-tumor activity and controllable safety in advanced or metastatic pancreatic ductal adenocarcinoma, and features of patients more likely to benefit from the combination were drawn.<\/jats:p>","DOI":"10.1038\/s41392-025-02530-2","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T08:21:57Z","timestamp":1766218917000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A phase 1b\/2 study of first-line anti-PD-L1\/ TGF-\u03b2RII fusion protein SHR-1701 combined with nab-paclitaxel and gemcitabine for advanced pancreatic ductal adenocarcinoma"],"prefix":"10.1038","volume":"10","author":[{"given":"Ran","family":"Xue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoyan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyun","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6697-7143","authenticated-orcid":false,"given":"Xianjun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8798-4756","authenticated-orcid":false,"given":"Lin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,20]]},"reference":[{"key":"2530_CR1","first-page":"17","volume":"73","author":"RL Siegel","year":"2023","unstructured":"Siegel, R. 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