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

Sep 23, 2026

Pancreatic ductal adenocarcinoma is an aggressive malignancy with limited effective therapies. Radiotherapy can convert PDAC from a “cold tumor” to a “hot tumor,” potentially improving immunotherapy response. Ivonescimab, a bispecific antibody targeting PD-1 and VEGF, is expected to enhance anti-PD-1/PD-L1 activity by shifting the tumor microenvironment to a more immune-permissive state, supporting combined treatment with SBRT and chemotherapy. The study evaluates efficacy and safety in locally advanced pancreatic cancer.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Background

Methods

Discussion

Tang et al. BMC Cancer (2025) 25:1581 BMC Cancer [https://doi.org/10.1186/s12885-025-14944-w](https://doi.org/10.1186/s12885-025-14944-w) STUDY PROTOCOL Open Access 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 Ziniu Tang 1, Fang Shi 1, Kunli Zhu 1, Rui Feng 1, Shumei Jiang 1, Minghuan Li 1*, Lei Xu 1* and Jinbo Yue 1* Abstract 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 period, establishing the recommended Phase II dose (RP2D) of Ivonescimab. In Phase II, the study aimed to investigate the median progression-free survival (mPFS) for patients with PDAC. The Phase II portion is a single-arm study utilizing the RP2D of Ivonescimab as determined in Phase Ib. Initially, participants will receive Ivonescimab in combination with SBRT (25-50 Gy/5F) over 2 weeks, followed by up to 8–10 cycles of Ivonescimab combined with modified FOLFIRINOX *Correspondence: Minghuan Li[sdlmh2014@163.com](sdlmh2014@163.com)[ ](sdlmh2014@163.com)Lei Xu [len.xu@hotmail.com](len.xu@hotmail.com)[ ](len.xu@hotmail.com)JinboYue[jbyue@sdfmu.edu.cn](jbyue@sdfmu.edu.cn) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/l](vecommons.org/l)icenses/by-nc-nd/4.0/. Tang et al. BMC Cancer (2025) 25:1581 Page 2 of 10 (mFOLFIRINOX; oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2 and fluorouracil 2400 mg/m2) . Maint

FAQs

What is the study’s main purpose for locally advanced pancreatic cancer?

To evaluate the efficacy and safety of Ivonescimab combined with adapted guided stereotactic body radiotherapy and chemotherapy in patients with locally advanced pancreatic cancer.

How is the trial structured across Phase Ib and Phase II?

Phase Ib is a dose-escalation design using a 3 + 3 methodology to determine MTD, DLT, and the recommended Phase II dose (RP2D). Phase II uses the RP2D from Phase Ib in a single-arm study to assess median progression-free survival (mPFS).

What treatment regimen is planned for participants during the study?

Participants receive Ivonescimab with SBRT (25–50 Gy/5F) over 2 weeks, followed by up to 8–10 cycles of Ivonescimab combined with modified FOLFIRINOX. Maintenance with Ivonescimab may continue up to 12 months based on tolerance or until progression or intolerable toxicity.

Sep 23, 2026

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