Radiotherapy combined with serplulimab, and chemotherapy as first-line treatment for metastatic pancreatic adenocarcinoma: a multicenter, single-arm, phase II trial

PURPOSE: The prognosis for metastatic pancreatic ductal adenocarcinoma (mPDAC) remains dismal. In this multicenter, single-arm, phase II study, we evaluated the combination of serplulimab, gemcitabine plus nab-paclitaxel, and radiotherapy (ICSBR regimen) as first-line treatment for mPDAC patients (ChiCTR2300073237). METHODS: Patients with mPDAC were enrolled in the first-line setting. The treatment regimen consisted of serplulimab and gemcitabine plus nab-paclitaxel administered in 21-day cycles, combined with stereotactic body radiotherapy directed at the primary or metastatic sites during cycle 2. Additionally, comprehensive biomarker analysis was conducted. The primary endpoint was the 6-month progression-free survival (PFS) rate, with a predefined target of 60%. RESULT: Forty-six patients received at least one dose of treatment. The 6-month PFS rate was 78.3% (95% CI, 67.2%-91.1%). The median PFS and overall survival (OS) were 8.5 months (95% CI, 7.3-12.0 months) and 14.0 months (95% CI, 12.0 months-not reached), respectively. The objective response rate was 73.9% (95% CI, 58.9%-85.7%). The combination treatment was well tolerated, and no treatment-related deaths or unexpected safety signals were observed. Notably, patients with baseline ctDNA negativity achieved a better survival. Moreover, tumor microenvironment (TME) analysis revealed that baseline fibroblast activation protein-positive cancer-associated fibroblast and T-cell proportions in tumor tissue correlated with clinical outcomes, with distinct spatial distribution and interaction tendencies observed among patients with different responses. CONCLUSION: Overall, the ICSBR regimen demonstrated a promising survival benefit as first-line treatment for mPDAC. Furthermore, ctDNA status and TME analysis highlighted potential markers for guiding precision treatment.

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Journal
Clinical Cancer Research
Published
2026-10-16
DOI
https://doi.org/10.1158/1078-0432.ccr-26-1824
Primary Topic
Pancreatic and Hepatic Oncology Research
Type
article
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article

Radiotherapy combined with serplulimab, and chemotherapy as first-line treatment for metastatic pancreatic adenocarcinoma: a multicenter, single-arm, phase II trial

Zixing Huang, Weikang Shao, Ke Cheng, Wenwu Ling et al.
Clinical Cancer Research
Pancreatic and Hepatic Oncology Research
article

Radiotherapy combined with serplulimab, and chemotherapy as first-line treatment for metastatic pancreatic adenocarcinoma: a multicenter, single-arm, phase II trial

Zixing Huang, Weikang Shao, Ke Cheng, Wenwu Ling, Gang Zhao, Qingqing Leng, Chengjian Zhao, Chenyan Zhang, Junjie Xiong, Wanting Hou, Hao Wei, Qiting Wu, Yi Cheng, Xiangbin Zhang, Ye Chen, Yi Zhang, Rui Wang, Zhiping Li, Ping Chen, Dan Cao, Du He, Chen Chang, Bole Tian, Yu Yang, Xiaofen Li, Xin You, Renming Zhong, Heqi Yang, Jitao Zhou, Jiaxin Liu, Ruizhen Li, Wenhao Guo, Xiaorui Zhu, Xiaoying Li, Pei Zhang, Huanji Xu
article en

Abstract

PURPOSE: The prognosis for metastatic pancreatic ductal adenocarcinoma (mPDAC) remains dismal. In this multicenter, single-arm, phase II study, we evaluated the combination of serplulimab, gemcitabine plus nab-paclitaxel, and radiotherapy (ICSBR regimen) as first-line treatment for mPDAC patients (ChiCTR2300073237). METHODS: Patients with mPDAC were enrolled in the first-line setting. The treatment regimen consisted of serplulimab and gemcitabine plus nab-paclitaxel administered in 21-day cycles, combined with stereotactic body radiotherapy directed at the primary or metastatic sites during cycle 2. Additionally, comprehensive biomarker analysis was conducted. The primary endpoint was the 6-month progression-free survival (PFS) rate, with a predefined target of 60%. RESULT: Forty-six patients received at least one dose of treatment. The 6-month PFS rate was 78.3% (95% CI, 67.2%-91.1%). The median PFS and overall survival (OS) were 8.5 months (95% CI, 7.3-12.0 months) and 14.0 months (95% CI, 12.0 months-not reached), respectively. The objective response rate was 73.9% (95% CI, 58.9%-85.7%). The combination treatment was well tolerated, and no treatment-related deaths or unexpected safety signals were observed. Notably, patients with baseline ctDNA negativity achieved a better survival. Moreover, tumor microenvironment (TME) analysis revealed that baseline fibroblast activation protein-positive cancer-associated fibroblast and T-cell proportions in tumor tissue correlated with clinical outcomes, with distinct spatial distribution and interaction tendencies observed among patients with different responses. CONCLUSION: Overall, the ICSBR regimen demonstrated a promising survival benefit as first-line treatment for mPDAC. Furthermore, ctDNA status and TME analysis highlighted potential markers for guiding precision treatment.

Clinical Cancer Research
Sichuan University (CN), West China Medical Center of Sichuan University (CN), West China Hospital of Sichuan University (CN), Chengdu University (CN), Seventh People's Hospital of Shanghai (CN), Genecast (China) (CN)
Good health and well-being
Openalex Percentile: Top 17%
Pancreatic and Hepatic Oncology Research
DOISourceOpenAlex
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