Clinical Trial

. 2024 Sep 19;9(1):248.

doi: 10.1038/s41392-024-01948-4.

Irinotecan hydrochloride liposome HR070803 in combination with 5-fluorouracil and leucovorin in locally advanced or metastatic pancreatic ductal adenocarcinoma following prior gemcitabine-based therapy (PAN-HEROIC-1): a phase 3 trial

Jiujie Cui^#¹, Shukui Qin^#², Yuhong Zhou³, Shuang Zhang⁴, Xiaofeng Sun⁵, Mingjun Zhang⁶, Jiuwei Cui⁷, Weijia Fang⁸, Kangsheng Gu⁹, Zhihua Li¹⁰, Jufeng Wang¹¹, Xiaobing Chen¹¹, Jun Yao¹², Jun Zhou¹³, Gang Wang¹⁴, Yuxian Bai¹⁵, Juxiang Xiao¹⁶, Wensheng Qiu¹⁷, Bangmao Wang¹⁸, Tao Xia¹⁹, Chunyue Wang²⁰, Li Kong²¹, Jiajun Yin²², Tao Zhang²³, Xionghu Shen²⁴, Deliang Fu²⁵, Chuntao Gao²⁶, Huan Wang²⁷, Quanren Wang²⁷, Liwei Wang²⁸

Affiliations

¹ Oncology Department and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
² GI Cancer Center, Nanjing Tianyinshan Hospital, China Pharmaceutical University, Nanjing, China. qinsk@csco.org.cn.
³ Medical Oncology, Zhongshan Hospital Affiliated with Fudan University, Shanghai, China.
⁴ Department of Biotherapy, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, China.
⁵ Internal Medicine, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
⁶ Medical Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
⁷ Department of Oncology, The First Hospital of Jilin University, Changchun, China.
⁸ Medical Oncology III, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁹ Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
¹⁰ Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
¹¹ Department of Oncology, The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, China.
¹² Department of Oncology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
¹³ Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
¹⁴ Department of Oncology, The First Affiliated Hospital of USTC Anhui Provincial Hospital, Hefei, China.
¹⁵ Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
¹⁶ Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
¹⁷ Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.
¹⁸ Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China.
¹⁹ Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, China.
²⁰ Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
²¹ Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
²² General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
²³ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
²⁴ Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, China.
²⁵ Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, China.
²⁶ Pancreatic Surgery, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China.
²⁷ Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
²⁸ Oncology Department and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. liweiwang@shsmu.edu.cn.

^# Contributed equally.

PMID: 39300077
PMCID: PMC11412970
DOI: 10.1038/s41392-024-01948-4

Clinical Trial

Irinotecan hydrochloride liposome HR070803 in combination with 5-fluorouracil and leucovorin in locally advanced or metastatic pancreatic ductal adenocarcinoma following prior gemcitabine-based therapy (PAN-HEROIC-1): a phase 3 trial

Jiujie Cui et al. Signal Transduct Target Ther. 2024.

. 2024 Sep 19;9(1):248.

doi: 10.1038/s41392-024-01948-4.

Authors

Affiliations

¹ Oncology Department and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
² GI Cancer Center, Nanjing Tianyinshan Hospital, China Pharmaceutical University, Nanjing, China. qinsk@csco.org.cn.
³ Medical Oncology, Zhongshan Hospital Affiliated with Fudan University, Shanghai, China.
⁴ Department of Biotherapy, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, China.
⁵ Internal Medicine, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
⁶ Medical Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
⁷ Department of Oncology, The First Hospital of Jilin University, Changchun, China.
⁸ Medical Oncology III, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁹ Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
¹⁰ Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
¹¹ Department of Oncology, The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, China.
¹² Department of Oncology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
¹³ Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
¹⁴ Department of Oncology, The First Affiliated Hospital of USTC Anhui Provincial Hospital, Hefei, China.
¹⁵ Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
¹⁶ Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
¹⁷ Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.
¹⁸ Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China.
¹⁹ Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, China.
²⁰ Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
²¹ Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
²² General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
²³ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
²⁴ Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, China.
²⁵ Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, China.
²⁶ Pancreatic Surgery, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China.
²⁷ Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
²⁸ Oncology Department and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. liweiwang@shsmu.edu.cn.

^# Contributed equally.

PMID: 39300077
PMCID: PMC11412970
DOI: 10.1038/s41392-024-01948-4

Abstract

Liposomal irinotecan has shown promising antitumor activity in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) who have undergone prior gemcitabine-based therapies. This randomized, double-blind, parallel-controlled, multicenter phase 3 study (NCT05074589) assessed the efficacy and safety of liposomal irinotecan HR070803 combined with 5-fluorouracil (5-FU) and leucovorin (LV) in this patient population. Patients with unresectable, locally advanced, or metastatic PDAC who had previously received gemcitabine-based therapies were randomized 1:1 to receive either HR070803 (60 mg/m² anhydrous irinotecan hydrochloride, equal to 56.5 mg/m² free base) or placebo, both in combination with 5-FU (2000 mg/m²) and LV (200 mg/m²), all given intravenously every two weeks. The primary endpoint of the study was overall survival (OS). A total of 298 patients were enrolled and received HR070803 plus 5-FU/LV (HR070803 group, n = 149) or placebo plus 5-FU/LV (placebo group, n = 149). Median OS was significantly improved in the HR070803 group compared to the placebo group (7.4 months [95% CI 6.1-8.4] versus 5.0 months [95% CI 4.3-6.0]; HR 0.63 [95% CI 0.48-0.84]; two-sided p = 0.0019). The most common grade ≥ 3 adverse events in the HR070803 group were increased gamma-glutamyltransferase (19.0% versus 11.6% in placebo group) and decreased neutrophil count (12.9% versus 0 in placebo group). No treatment-related deaths occurred in the HR070803 group, while the placebo group reported one treatment-related death (abdominal infection). HR070803 in combination with 5-FU/LV has shown promising efficacy and manageable safety in advanced or metastatic PDAC in the second-line setting, representing a potential option in this patient population.

PubMed Disclaimer

Conflict of interest statement

H.W. and Q.W. are employees of Jiangsu Hengrui Pharmaceuticals. The remaining authors declare no competing interests.

Figures

**Fig. 2**
OS. (a) Kaplan-Meier plot of OS. (b) Subgroup analysis. *It indicates the number of patients who were diagnosed with stage IV at the initial pancreatic cancer diagnosis, not during the enrollment period of this study

**Fig. 3**
Kaplan-Meier plots of PFS and TTF (a) PFS. (b) TTF

See this image and copyright information in PMC

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Irinotecan hydrochloride liposome HR070803 in combination with 5-fluorouracil and leucovorin in locally advanced or metastatic pancreatic ductal adenocarcinoma following prior gemcitabine-based therapy (PAN-HEROIC-1): a phase 3 trial

Affiliations

Irinotecan hydrochloride liposome HR070803 in combination with 5-fluorouracil and leucovorin in locally advanced or metastatic pancreatic ductal adenocarcinoma following prior gemcitabine-based therapy (PAN-HEROIC-1): a phase 3 trial

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