Study protocol for a single-arm phase Ib/II trial of Ivonescimab combined with adapted guided stereotactic body radiotherapy and chemotherapy in patients with locally advanced pancreatic cancer

作者：Ziniu Tang, Shi Fang, Kunli Zhu, Rui Feng, Shumei Jiang, Minghuan Li, Lei Xu, Jinbo Yue · 发表于：BMC Cancer · 年份：2025 · DOI：10.1186/s12885-025-14944-w · 被引用次数：1 · 研究领域：Pancreatic and Hepatic Oncology Research、Neuroendocrine Tumor Research Advances、Lung Cancer Research Studies

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited effective treatment options, contributing to its high mortality of rate. Radiotherapy has shown effect in converting PDAC from a "cold tumor" to "hot tumor”, thus enhancing its response to immunotherapy. The synergistic effect of radiotherapy and immunotherapy may further improve therapeutic efficacy. Additionally, studies have demonstrated that vascular endothelial growth factor (VEGF) inhibitors can enhance the effectiveness of anti-programmed cell death 1/ligand 1 (anti-PD-1/PD-L1) antibodies by transforming the immunosuppressive tumor microenvironment (TME) into an immune-permissive TME. This study aims to investigate the efficacy and safety of Ivonescimab-a bispecific antibody against programmed cell death protein 1 and VEGF-in combined with stereotactic body radiotherapy (SBRT) and chemotherapy for treating locally advanced pancreatic cancer (LAPC). METHODS: This is a single-arm, Phase Ib/II clinical study designed to recruit 37 patients with LAPC (NCT06844422). Before enrollment, participants must undergo a comprehensive clinical evaluation, including imaging and cytological or histopathological examinations. The objective of Phase Ib was to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended Phase II dose (RP2D) of Ivonescimab. The Phase Ib component follows a dose-escalation design using a 3 + 3 methodology to deterime DLT over 4-week...