A phase I study of toripalimab, an anti‐PD‐1 antibody, in patients with refractory malignant solid tumors
Abstract Background Several programmed cell death ligand 1 (PD‐L1)/programmed cell death protein 1 (PD‐1) antibodies have been approved for cancer treatment worldwide. Their pharmacokinetic and pharmacodynamic characteristics have been reported mainly in western countries, but related data in Chines...
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| Format: | Article |
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Wiley
2020-08-01
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| Series: | Cancer Communications |
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| Online Access: | https://doi.org/10.1002/cac2.12068 |
| _version_ | 1818148171807719424 |
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| author | Xiao‐Li Wei Chao Ren Feng‐Hua Wang Yang Zhang Hong‐Yun Zhao Ben‐Yan Zou Zhi‐Qiang Wang Miao‐Zhen Qiu Dong‐Sheng Zhang Hui‐Yan Luo Feng Wang Sheng Yao Rui‐Hua Xu |
| author_facet | Xiao‐Li Wei Chao Ren Feng‐Hua Wang Yang Zhang Hong‐Yun Zhao Ben‐Yan Zou Zhi‐Qiang Wang Miao‐Zhen Qiu Dong‐Sheng Zhang Hui‐Yan Luo Feng Wang Sheng Yao Rui‐Hua Xu |
| author_sort | Xiao‐Li Wei |
| collection | DOAJ |
| description | Abstract Background Several programmed cell death ligand 1 (PD‐L1)/programmed cell death protein 1 (PD‐1) antibodies have been approved for cancer treatment worldwide. Their pharmacokinetic and pharmacodynamic characteristics have been reported mainly in western countries, but related data in Chinese patients are limited. This study was conducted to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamics of an anti‐PD‐1 antibody, toripalimab, in Chinese patients. Methods A single‐center phase I study was conducted in Sun Yat‐sen University Cancer Center. Eligible patients were adults with histologically confirmed, treatment‐refractory, advanced, solitary malignant tumors. Toripalimab was intravenously infused every 2 weeks in dose‐escalating cohorts at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg. The study followed standard 3 + 3 design. Results Between 15th March 2016 and 27th September 2016, 25 patients were enrolled, of whom 3 (12.0%), 7 (28.0%), 6 (24.0%), 6 (24.0%), 3 (12.0%) received 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg toripalimab, respectively. After a median follow‐up time of 5.0 months (range: 1.5‐19.8 months), we observed that the commonest treatment‐related adverse events (TRAEs) were fatigue (64.0%) and rash (24.0%). No grade 3 or higher TRAEs were observed. No dose‐limiting toxicity, treatment‐related serious adverse events (SAEs), or treatment‐related death occurred. Objective response rate was 12.5%. The half‐life of toripalimab was 150‐222 h after a single dose infusion. Most patients, including those from the 0.3 mg/kg group, maintained complete PD‐1 receptor occupancy (> 80%) on activated T cells since receiving the first dose of toripalimab. Conclusions Toripalimab is a promising anti‐PD‐1 antibody, which was well tolerated and demonstrated anti‐tumor activity in treatment‐refractory advanced solitary malignant tumors. Further exploration in various tumors and combination therapies is warranted. |
| first_indexed | 2024-12-11T12:46:54Z |
| format | Article |
| id | doaj.art-8ce01e25a806447a911986d71c98652a |
| institution | Directory Open Access Journal |
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| last_indexed | 2024-12-11T12:46:54Z |
| publishDate | 2020-08-01 |
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| series | Cancer Communications |
| spelling | doaj.art-8ce01e25a806447a911986d71c98652a2022-12-22T01:06:48ZengWileyCancer Communications2523-35482020-08-0140834535410.1002/cac2.12068A phase I study of toripalimab, an anti‐PD‐1 antibody, in patients with refractory malignant solid tumorsXiao‐Li Wei0Chao Ren1Feng‐Hua Wang2Yang Zhang3Hong‐Yun Zhao4Ben‐Yan Zou5Zhi‐Qiang Wang6Miao‐Zhen Qiu7Dong‐Sheng Zhang8Hui‐Yan Luo9Feng Wang10Sheng Yao11Rui‐Hua Xu12Department of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 P. R. ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 P. R. ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 P. R. ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 P. R. ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 P. R. ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 P. R. ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 P. R. ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 P. R. ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 P. R. ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 P. R. ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 P. R. ChinaShanghai Junshi Biosciences Company Limited Shanghai 201203 P. R. ChinaDepartment of Medical Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 P. R. ChinaAbstract Background Several programmed cell death ligand 1 (PD‐L1)/programmed cell death protein 1 (PD‐1) antibodies have been approved for cancer treatment worldwide. Their pharmacokinetic and pharmacodynamic characteristics have been reported mainly in western countries, but related data in Chinese patients are limited. This study was conducted to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamics of an anti‐PD‐1 antibody, toripalimab, in Chinese patients. Methods A single‐center phase I study was conducted in Sun Yat‐sen University Cancer Center. Eligible patients were adults with histologically confirmed, treatment‐refractory, advanced, solitary malignant tumors. Toripalimab was intravenously infused every 2 weeks in dose‐escalating cohorts at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg. The study followed standard 3 + 3 design. Results Between 15th March 2016 and 27th September 2016, 25 patients were enrolled, of whom 3 (12.0%), 7 (28.0%), 6 (24.0%), 6 (24.0%), 3 (12.0%) received 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg toripalimab, respectively. After a median follow‐up time of 5.0 months (range: 1.5‐19.8 months), we observed that the commonest treatment‐related adverse events (TRAEs) were fatigue (64.0%) and rash (24.0%). No grade 3 or higher TRAEs were observed. No dose‐limiting toxicity, treatment‐related serious adverse events (SAEs), or treatment‐related death occurred. Objective response rate was 12.5%. The half‐life of toripalimab was 150‐222 h after a single dose infusion. Most patients, including those from the 0.3 mg/kg group, maintained complete PD‐1 receptor occupancy (> 80%) on activated T cells since receiving the first dose of toripalimab. Conclusions Toripalimab is a promising anti‐PD‐1 antibody, which was well tolerated and demonstrated anti‐tumor activity in treatment‐refractory advanced solitary malignant tumors. Further exploration in various tumors and combination therapies is warranted.https://doi.org/10.1002/cac2.12068anti‐PD‐1 antibodytoripalimabphase I studysafetyefficacypharmacokinetics |
| spellingShingle | Xiao‐Li Wei Chao Ren Feng‐Hua Wang Yang Zhang Hong‐Yun Zhao Ben‐Yan Zou Zhi‐Qiang Wang Miao‐Zhen Qiu Dong‐Sheng Zhang Hui‐Yan Luo Feng Wang Sheng Yao Rui‐Hua Xu A phase I study of toripalimab, an anti‐PD‐1 antibody, in patients with refractory malignant solid tumors Cancer Communications anti‐PD‐1 antibody toripalimab phase I study safety efficacy pharmacokinetics |
| title | A phase I study of toripalimab, an anti‐PD‐1 antibody, in patients with refractory malignant solid tumors |
| title_full | A phase I study of toripalimab, an anti‐PD‐1 antibody, in patients with refractory malignant solid tumors |
| title_fullStr | A phase I study of toripalimab, an anti‐PD‐1 antibody, in patients with refractory malignant solid tumors |
| title_full_unstemmed | A phase I study of toripalimab, an anti‐PD‐1 antibody, in patients with refractory malignant solid tumors |
| title_short | A phase I study of toripalimab, an anti‐PD‐1 antibody, in patients with refractory malignant solid tumors |
| title_sort | phase i study of toripalimab an anti pd 1 antibody in patients with refractory malignant solid tumors |
| topic | anti‐PD‐1 antibody toripalimab phase I study safety efficacy pharmacokinetics |
| url | https://doi.org/10.1002/cac2.12068 |
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