{"doi":"10.1038/s41392-024-01857-6","title":"First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial","abstract":"<jats:title>Abstract</jats:title><jats:p>Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4–62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3–99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1–11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.</jats:p>","journal":"Signal Transduction and Targeted Therapy","year":2024,"id":651192,"datarank":0.5456379239589579,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"self_citation_contribution":0.5456379239589579,"citation_network_contribution":0.0,"self_endowment_contribution":0.5456379239589579,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":53186,"name":"Fan Tong","orcid":null,"position":1,"is_corresponding":false},{"id":1698194,"name":"Jiayao Ni","orcid":null,"position":2,"is_corresponding":false},{"id":1428959,"name":"Yi Sun","orcid":"0000-0002-0210-4730","position":3,"is_corresponding":false},{"id":1032417,"name":"Yahui Zhu","orcid":"0000-0001-9444-5454","position":4,"is_corresponding":false},{"id":839700,"name":"Liang Qi","orcid":"0000-0002-2155-2061","position":5,"is_corresponding":false},{"id":155069,"name":"Xiaoqin Li","orcid":null,"position":6,"is_corresponding":false},{"id":717111,"name":"Wei Li","orcid":"0000-0002-7530-4872","position":7,"is_corresponding":false},{"id":1392778,"name":"Yan Yang","orcid":"0000-0001-5719-043X","position":8,"is_corresponding":false},{"id":1464521,"name":"Qing Gu","orcid":"0000-0003-3855-3690","position":9,"is_corresponding":false},{"id":799960,"name":"Xing Zhang","orcid":"0000-0003-4315-6980","position":10,"is_corresponding":false},{"id":1161098,"name":"Xiaoxuan Wang","orcid":"0000-0002-0501-1521","position":11,"is_corresponding":false},{"id":1698200,"name":"Chan Zhu","orcid":null,"position":12,"is_corresponding":false},{"id":564624,"name":"Dongsheng Chen","orcid":"0000-0003-2005-2353","position":13,"is_corresponding":false},{"id":437440,"name":"Baorui Liu","orcid":"0000-0002-2539-7732","position":14,"is_corresponding":false},{"id":1191961,"name":"Juan Du","orcid":"0000-0003-0192-6633","position":15,"is_corresponding":false},{"id":437445,"name":"Huizi Sha","orcid":"0000-0001-6820-8885","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial","abstract":"<jats:title>Abstract</jats:title><jats:p>Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4–62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3–99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1–11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. 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