Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial
Background Immune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the po...
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001240.full |
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| author | Jian Wang Hao Wu Jing Sun Xiao Li Yongqian Shu Xiaofeng Wu Guoqiang Wang Huajun Li Xiaofeng Chen Yanhong Gu Yang Shao Qianwen Shao Feipeng Zhu Xiaofeng Qian Jun Hu Fengjiao Zhao Weidong Mao Gaohua Han Changxian Li Yongxiang Xia Poshita Kumari Seesaha Dongqin Zhu Junling Zhang Xuehao Wang Xiangcheng Li |
| author_facet | Jian Wang Hao Wu Jing Sun Xiao Li Yongqian Shu Xiaofeng Wu Guoqiang Wang Huajun Li Xiaofeng Chen Yanhong Gu Yang Shao Qianwen Shao Feipeng Zhu Xiaofeng Qian Jun Hu Fengjiao Zhao Weidong Mao Gaohua Han Changxian Li Yongxiang Xia Poshita Kumari Seesaha Dongqin Zhu Junling Zhang Xuehao Wang Xiangcheng Li |
| author_sort | Jian Wang |
| collection | DOAJ |
| description | Background Immune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response.Methods In this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m2) and oxaliplatin (85 mg/m2). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment.Results 54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS <1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p>0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28).Conclusion Camrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX.Trial registration number NCT03486678. |
| format | Article |
| id | doaj-art-d5f328793454453394cb0cfdd3fceec0 |
| institution | OA Journals |
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| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-d5f328793454453394cb0cfdd3fceec02025-08-20T02:13:22ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001240Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trialJian Wang0Hao Wu1Jing Sun2Xiao Li3Yongqian Shu4Xiaofeng Wu5Guoqiang Wang6Huajun Li7Xiaofeng Chen8Yanhong Gu9Yang Shao10Qianwen Shao11Feipeng Zhu12Xiaofeng Qian13Jun Hu14Fengjiao Zhao15Weidong Mao16Gaohua Han17Changxian Li18Yongxiang Xia19Poshita Kumari Seesaha20Dongqin Zhu21Junling Zhang22Xuehao Wang23Xiangcheng Li24Department of Pain Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China2Department of Radiology, Capital Medical University Affiliated Beijing Friendship Hospital, ChinaIntensive Care Unit, Nanjing Drum Tower Hospital, Nanjing, ChinaCollaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China7 Shenyang Sixth People’s Hospital, Shenyang, Liaoning, ChinaIntensive care uinits, Lanzhou University First Affiliated Hospital, Lanzhou, ChinaMedical Department, Jiangsu Hengrui Medicine Co Ltd, Lianyungang, ChinaDepartment of Periodontology, Shanghai Stomatological Hospital & School of Somatology, Fudan University, Shanghai, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaMedical Department, Nanjing Geneseeq Technology Inc, Nanjing, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaShandong University of Traditional Chinese Medicine, Jinan, Shandong, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, Jiangyin People’s Hospital, Jiangyin, ChinaDepartment of Oncology, Taizhou People`s Hospital Affiliated to Nantong University, Taizhou, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaMedical Department, Nanjing Geneseeq Technology Inc, Nanjing, ChinaMedical Department, 3D Medicines Inc, Shanghai, ChinaHepatobiliary/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Transplantation, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaBackground Immune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response.Methods In this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m2) and oxaliplatin (85 mg/m2). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment.Results 54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS <1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p>0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28).Conclusion Camrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX.Trial registration number NCT03486678.https://jitc.bmj.com/content/8/2/e001240.full |
| spellingShingle | Jian Wang Hao Wu Jing Sun Xiao Li Yongqian Shu Xiaofeng Wu Guoqiang Wang Huajun Li Xiaofeng Chen Yanhong Gu Yang Shao Qianwen Shao Feipeng Zhu Xiaofeng Qian Jun Hu Fengjiao Zhao Weidong Mao Gaohua Han Changxian Li Yongxiang Xia Poshita Kumari Seesaha Dongqin Zhu Junling Zhang Xuehao Wang Xiangcheng Li Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial Journal for ImmunoTherapy of Cancer |
| title | Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial |
| title_full | Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial |
| title_fullStr | Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial |
| title_full_unstemmed | Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial |
| title_short | Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial |
| title_sort | camrelizumab plus gemcitabine and oxaliplatin gemox in patients with advanced biliary tract cancer a single arm open label phase ii trial |
| url | https://jitc.bmj.com/content/8/2/e001240.full |
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