The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial
Abstract This open-label phase II trial (NCT04542837) aimed to evaluate the efficacy and safety of KN046 combined with lenvatinib in patients with advanced hepatocellular carcinoma (HCC), and explore the potential response biomarkers. Participants received KN046 5 mg/kg every 3 weeks and lenvatinib...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56537-y |
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| author | Da Xu Hongwei Wang Quan Bao Kemin Jin Ming Liu Wei Liu Xiaoluan Yan Lijun Wang Yanqiao Zhang Guangyu Wang Yue Ma Zhigang Ma Chunhui Zhang Jiebing Tang Sha Wang Jiaohui Pang Ting Xu Kun Wang Baocai Xing |
| author_facet | Da Xu Hongwei Wang Quan Bao Kemin Jin Ming Liu Wei Liu Xiaoluan Yan Lijun Wang Yanqiao Zhang Guangyu Wang Yue Ma Zhigang Ma Chunhui Zhang Jiebing Tang Sha Wang Jiaohui Pang Ting Xu Kun Wang Baocai Xing |
| author_sort | Da Xu |
| collection | DOAJ |
| description | Abstract This open-label phase II trial (NCT04542837) aimed to evaluate the efficacy and safety of KN046 combined with lenvatinib in patients with advanced hepatocellular carcinoma (HCC), and explore the potential response biomarkers. Participants received KN046 5 mg/kg every 3 weeks and lenvatinib 12 or 8 mg once daily. The primary endpoints were safety, tolerability, dose-limiting toxicity (DLT), and objective response rate (ORR) according to RECIST v1.1. A total of fifty-five participants were enrolled. The results meet the pre-specified primary endpoints. No DLT was observed in the safety run-in period. The incidence of serious adverse events and grade ≥3 treatment-related adverse events (TRAEs) was 30.9% and 47.3%, respectively. Grade ≥3 immunotherapy-related adverse events occurred in 3 (5.5%) participants. Five (9.1%) participants discontinued treatment due to TRAEs, all of which were grade 1-2. The ORR was 45.5% (95% CI, 31.97-59.45). The median progression-free survival was 11.0 (95% CI, 8.21-15.24) months. The median overall survival (OS) was 16.4 (95% CI, 11.20-not estimable) months, and 12-month OS rate was 60.0% (95% CI, 45.87-71.55). Circulating tumor DNA status before the third cycle of treatment was associated with prognosis. In conclusion, First-line KN046 plus lenvatinib shows promising efficacy for advanced unresectable or metastatic HCC. |
| format | Article |
| id | doaj-art-16ec6c8793e54cf68fa1f34369e0554f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-16ec6c8793e54cf68fa1f34369e0554f2025-02-09T12:45:29ZengNature PortfolioNature Communications2041-17232025-02-0116111110.1038/s41467-025-56537-yThe anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trialDa Xu0Hongwei Wang1Quan Bao2Kemin Jin3Ming Liu4Wei Liu5Xiaoluan Yan6Lijun Wang7Yanqiao Zhang8Guangyu Wang9Yue Ma10Zhigang Ma11Chunhui Zhang12Jiebing Tang13Sha Wang14Jiaohui Pang15Ting Xu16Kun Wang17Baocai Xing18Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepatopancreatobiliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepatopancreatobiliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepatopancreatobiliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepatopancreatobiliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepatopancreatobiliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepatopancreatobiliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepatopancreatobiliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepatopancreatobiliary Surgery, Peking University Cancer Hospital & InstituteDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer HospitalDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer HospitalDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer HospitalDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer HospitalDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer HospitalDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer HospitalGeneseeq Research Institute, Nanjing Geneseeq Technology Inc.Geneseeq Research Institute, Nanjing Geneseeq Technology Inc.Jiangsu Alphamab Biopharmaceuticals Co. LtdKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepatopancreatobiliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepatopancreatobiliary Surgery, Peking University Cancer Hospital & InstituteAbstract This open-label phase II trial (NCT04542837) aimed to evaluate the efficacy and safety of KN046 combined with lenvatinib in patients with advanced hepatocellular carcinoma (HCC), and explore the potential response biomarkers. Participants received KN046 5 mg/kg every 3 weeks and lenvatinib 12 or 8 mg once daily. The primary endpoints were safety, tolerability, dose-limiting toxicity (DLT), and objective response rate (ORR) according to RECIST v1.1. A total of fifty-five participants were enrolled. The results meet the pre-specified primary endpoints. No DLT was observed in the safety run-in period. The incidence of serious adverse events and grade ≥3 treatment-related adverse events (TRAEs) was 30.9% and 47.3%, respectively. Grade ≥3 immunotherapy-related adverse events occurred in 3 (5.5%) participants. Five (9.1%) participants discontinued treatment due to TRAEs, all of which were grade 1-2. The ORR was 45.5% (95% CI, 31.97-59.45). The median progression-free survival was 11.0 (95% CI, 8.21-15.24) months. The median overall survival (OS) was 16.4 (95% CI, 11.20-not estimable) months, and 12-month OS rate was 60.0% (95% CI, 45.87-71.55). Circulating tumor DNA status before the third cycle of treatment was associated with prognosis. In conclusion, First-line KN046 plus lenvatinib shows promising efficacy for advanced unresectable or metastatic HCC.https://doi.org/10.1038/s41467-025-56537-y |
| spellingShingle | Da Xu Hongwei Wang Quan Bao Kemin Jin Ming Liu Wei Liu Xiaoluan Yan Lijun Wang Yanqiao Zhang Guangyu Wang Yue Ma Zhigang Ma Chunhui Zhang Jiebing Tang Sha Wang Jiaohui Pang Ting Xu Kun Wang Baocai Xing The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial Nature Communications |
| title | The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial |
| title_full | The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial |
| title_fullStr | The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial |
| title_full_unstemmed | The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial |
| title_short | The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial |
| title_sort | anti pd l1 ctla 4 bispecific antibody kn046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma a phase ii trial |
| url | https://doi.org/10.1038/s41467-025-56537-y |
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