{ "abstract": "Background: The clinical benefit of combining chemotherapy with immunotherapy in metastatic triple-negative breast cancer (TNBC) varies depending on the chemotherapy backbone, highlighting the need for optimizing combination partners. This single-arm exploratory phase II trial evaluated the efficacy and safety of sintilimab combined with eribulin and carboplatin (ErCb) in patients with metastatic TNBC previously treated with anthracyclines and/or taxanes.\n\nMethods: Eligible patients received eribulin 1.4 mg/m2 and carboplatin (area under the curve=2) on days 1 and 8, plus sintilimab 200 mg on day 8 of each 21-day cycle. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2400082647).\n\nResults: Between February 2024 and March 2025, 27 female patients were enrolled. All patients had received prior treatment with anthracyclines and/or taxane-based chemotherapy. 18 patients (66.7%) had ≥3 metastatic lesions, 19 (70.4%) had visceral metastases, and 5 (18.5%) had brain metastases (BM). The confirmed ORR was 70.4% and DCR was 81.5%. At a median follow-up of 16.2 months, median PFS was 7.6 months; median OS was immature at 19.0 months, with only 33.3% of events reported. Notably, all five patients with BM achieved a partial response in both intracranial and systemic lesions. In an exploratory multivariate analysis, Eastern Cooperative Oncology Group performance status 1, ≥3 metastatic sites, and programmed cell death-ligand 1 negativity were potentially associated with worse PFS. The most common grade ≥3 adverse events (AEs) were neutropenia (48.1%), febrile neutropenia (14.8%), and thrombocytopenia (7.4%), stomatitis (3.7%), and aspartate aminotransferase/aspartate aminotransferase elevation (3.7%). Hypothyroidism (18.5%) was the most common immunotherapy-related adverse event (irAE), with no grade ≥3 irAEs observed. Exploratory biomarker analyses suggested that higher baseline CXCL10, CCL28, CD58, and CD99 levels were associated with longer survival, whereas insulin-like growth factor-binding trended downward at progression. RNA-sequencing data revealed enrichment of the hypoxia-inducible factor 1 (HIF-1) pathway in poor responders and at progression.\n\nConclusion: In this exploratory phase II trial, sintilimab plus ErCb showed promising preliminary antitumor activity and a manageable safety profile in patients with anthracycline-pretreated and/or taxane-pretreated metastatic TNBC. These hypothesis-generating findings support further evaluation in larger, randomized controlled trials.\n\nTrial registration number: ChiCTR2400082647.", "abstract_shown": true, "affiliations": [ "Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China", "Cancer Hospital, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China", "Department of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China", "Department of Breast, Bone and Soft Tissue Oncology, Guangxi Medical University Cancer Hospital, Nanning, China" ], "article_type": "research article", "arxiv": null, "author_total": 17, "authors": [ { "affs": [ 0 ], "name": "Mengqian Ni" }, { "affs": [ 0 ], "name": "Lijia Zhou" }, { "affs": [ 0 ], "name": "Lulu Zhang" }, { "affs": [ 0 ], "name": "Yanhong Su" }, { "affs": [ 1 ], "name": "Huadi Shi" }, { "affs": [ 0 ], "name": "Meiting Chen", "orcid": "0000-0002-7195-1300" }, { "affs": [ 0 ], "name": "Qiufang Zheng" }, { "affs": [ 0 ], "name": "Haifeng Li" }, { "affs": [ 0 ], "name": "Daining Wang" }, { "affs": [ 0 ], "name": "Shu Dun" }, { "affs": [ 0 ], "name": "Qingru Zhou" }, { "affs": [ 2 ], "name": "Peng Sun" }, { "affs": [ 1 ], "name": "Lixia Li" }, { "affs": [ 0 ], "name": "Shusen Wang" }, { "affs": [ 3 ], "name": "Yongkui Lu" }, { "affs": [ 0 ], "name": "Yanxia Shi", "orcid": "0000-0002-5414-8049" }, { "affs": [ 0 ], "name": "Xin An", "orcid": "0000-0003-0683-5511" } ], "bibtex": "https://research.draconitic.com/paper/bvasve2mzqy1s.bib", "cited_by": 0, "doi": "10.1136/jitc-2026-016269", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711526/", "id": "bvasve2mzqy1s", "issns": [ "2051-1426" ], "landing_url": "https://doi.org/10.1136/jitc-2026-016269", "language": "en", "licence": "CC-BY-NC-4.0", "licence_label": "CC BY-NC 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "1506" ], [ "heading", "Clinical Cancer Immunotherapy" ], [ "heading", "Original Research" ], [ "openalex", "2730|Cancer Immunotherapy and Biomarkers" ] ], "openalex": "W7223392355", "pdf_url": null, "pmcid": "PMC13711526", "pmid": "42919625", "published": "2026-10-23", "publisher": "BMJ Publishing Group", "ris": "https://research.draconitic.com/paper/bvasve2mzqy1s.ris", "sources": [ { "first_seen": "2026-10-31T12:22:17Z", "native_id": "PMC13711526", "source": "pmc", "url": "https://doi.org/10.1136/jitc-2026-016269" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers", "subfield": "oncology" } ], "title": "Sintilimab plus eribulin and carboplatin in patients with metastatic triple-negative breast cancer (SECURE): a phase II, multicenter trial", "title_text": "Sintilimab plus eribulin and carboplatin in patients with metastatic triple-negative breast cancer (SECURE): a phase II, multicenter trial", "type": "peer-reviewed", "updated_at": "2026-10-31T12:22:17Z", "url": "https://research.draconitic.com/paper/bvasve2mzqy1s", "venue": "Journal for Immunotherapy of Cancer", "versions": [] }