Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial
Abstract Purpose Open-label phase Ib/II study to investigate the safety and efficacy of LBL-007, an anti-LAG-3 antibody, plus toripalimab, an anti-PD-1 antibody, in patients with previously treated advanced nasopharyngeal carcinoma (NPC) and other solid tumors. Methods Patients with advanced tumors...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | Journal of Hematology & Oncology |
| Online Access: | https://doi.org/10.1186/s13045-025-01666-6 |
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| author | Gang Chen Dong-Chen Sun Yi Ba Ya-Xiong Zhang Ting Zhou Yuan-Yuan Zhao Hong-Yun Zhao Wen-Feng Fang Yan Huang Zhen Wang Chao Deng De-Sheng Hu Wei Wang Jin-Guan Lin Gui-Ling Li Su-Xia Luo Zhi-Chao Fu Hai-Sheng Zhu Hui-Li Wang Sheng-Li Cai Xiao-Qiang Kang Li Zhang Yun-Peng Yang |
| author_facet | Gang Chen Dong-Chen Sun Yi Ba Ya-Xiong Zhang Ting Zhou Yuan-Yuan Zhao Hong-Yun Zhao Wen-Feng Fang Yan Huang Zhen Wang Chao Deng De-Sheng Hu Wei Wang Jin-Guan Lin Gui-Ling Li Su-Xia Luo Zhi-Chao Fu Hai-Sheng Zhu Hui-Li Wang Sheng-Li Cai Xiao-Qiang Kang Li Zhang Yun-Peng Yang |
| author_sort | Gang Chen |
| collection | DOAJ |
| description | Abstract Purpose Open-label phase Ib/II study to investigate the safety and efficacy of LBL-007, an anti-LAG-3 antibody, plus toripalimab, an anti-PD-1 antibody, in patients with previously treated advanced nasopharyngeal carcinoma (NPC) and other solid tumors. Methods Patients with advanced tumors refractory to prior standard therapies were enrolled. In phase Ib, patients received LBL-007 200 mg or 400 mg and toripalimab 240 mg intravenously once every 3 weeks. In phase II, all patients received LBL-007 at the recommended phase II dose (RP2D) and toripalimab 240 mg intravenously once every 3 weeks. The primary end points were safety in phase Ib and objective response rate (ORR) in phase II. The exploratory end point was the predictive capability of LAG-3 and PD-L1 expression for efficacy. Results Between November 30, 2021, and December 1, 2023, 80 patients were enrolled, including 30 (37.5%) with NPC and 50 (62.5%) with other tumors. Median follow-up was 26.0 months. In Phase Ib, LBL-007 was administered at 200 mg to four patients and 400 mg to six patients, with no dose-limiting toxicities observed. Therefore, the 400 mg dose of LBL-007 was established as the RP2D and administered to 70 patients in phase II. Nine (11.3%) of 80 patients had grade 3 or 4 treatment-related adverse events, the most common of which included anemia (2.5%), hyponatremia (2.5%), increased alanine aminotransferase (2.5%), increased aspartate aminotransferase (1.3%), and fatigue (1.3%). Eight patients (10.0%) had treatment-related serious adverse events. No treatment-related deaths were reported. In immunotherapy-naive NPC patients (n = 12), ORR was 33.3%, disease control rate (DCR) was 75%, and median progression-free survival (PFS) was 10.8 months (95% CI, 1.3 to not estimated). In IO-treated NPC patients (n = 17), ORR was 11.8%, DCR was 64.7%, and median PFS was 2.7 months (95% CI, 1.4 to 4.9). For other tumors, ORRs were 15.8% in immunotherapy-naive patients and 3.7% in immunotherapy-treated patients. Patients with ≥ 2 + LAG-3 expression had a higher ORR of 28.0%, compared to 7.7% in those with < 2 + LAG-3 expression. Conclusion LBL-007 plus toripalimab exhibited a manageable safety profile in patients with advanced solid tumors and demonstrated promising antitumor activity in NPC, especially in immunotherapy-naive patients. These findings warrant further validation in future studies. |
| format | Article |
| id | doaj-art-65b9060aaf7944e6baac43e492a33e6f |
| institution | Kabale University |
| issn | 1756-8722 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj-art-65b9060aaf7944e6baac43e492a33e6f2025-02-09T12:51:21ZengBMCJournal of Hematology & Oncology1756-87222025-02-0118111010.1186/s13045-025-01666-6Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trialGang Chen0Dong-Chen Sun1Yi Ba2Ya-Xiong Zhang3Ting Zhou4Yuan-Yuan Zhao5Hong-Yun Zhao6Wen-Feng Fang7Yan Huang8Zhen Wang9Chao Deng10De-Sheng Hu11Wei Wang12Jin-Guan Lin13Gui-Ling Li14Su-Xia Luo15Zhi-Chao Fu16Hai-Sheng Zhu17Hui-Li Wang18Sheng-Li Cai19Xiao-Qiang Kang20Li Zhang21Yun-Peng Yang22Department of Medical Oncology, Sun Yat-sen University Cancer CenterDepartment of Medical Oncology, Sun Yat-sen University Cancer CenterDepartment of Gastrointestinal Oncology, Tianjin Medical University Cancer Institute and HospitalDepartment of Medical Oncology, Sun Yat-sen University Cancer CenterDepartment of Medical Oncology, Sun Yat-sen University Cancer CenterDepartment of Medical Oncology, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer CenterDepartment of Medical Oncology, Sun Yat-sen University Cancer CenterDepartment of Medical Oncology, Sun Yat-sen University Cancer CenterDepartment of Oncology, Linyi Cancer HospitalCancer Center, Chong Qing University Three Gorges HospitalDepartment of Radiation Oncology, Hubei Cancer HospitalHunan Cancer HospitalHunan Cancer HospitalCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Henan Cancer HospitalDepartment of Radiotherapy, No. 900 Hospital of the PLA Joint Logistics Support ForceDepartment of Oncology, The First People’s Hospital of YulinDepartment of Oncology, Affiliated Hospital of Jining Medical UniversityNanjing Leads Biolabs Co., Ltd.Nanjing Leads Biolabs Co., Ltd.Department of Medical Oncology, Sun Yat-sen University Cancer CenterDepartment of Medical Oncology, Sun Yat-sen University Cancer CenterAbstract Purpose Open-label phase Ib/II study to investigate the safety and efficacy of LBL-007, an anti-LAG-3 antibody, plus toripalimab, an anti-PD-1 antibody, in patients with previously treated advanced nasopharyngeal carcinoma (NPC) and other solid tumors. Methods Patients with advanced tumors refractory to prior standard therapies were enrolled. In phase Ib, patients received LBL-007 200 mg or 400 mg and toripalimab 240 mg intravenously once every 3 weeks. In phase II, all patients received LBL-007 at the recommended phase II dose (RP2D) and toripalimab 240 mg intravenously once every 3 weeks. The primary end points were safety in phase Ib and objective response rate (ORR) in phase II. The exploratory end point was the predictive capability of LAG-3 and PD-L1 expression for efficacy. Results Between November 30, 2021, and December 1, 2023, 80 patients were enrolled, including 30 (37.5%) with NPC and 50 (62.5%) with other tumors. Median follow-up was 26.0 months. In Phase Ib, LBL-007 was administered at 200 mg to four patients and 400 mg to six patients, with no dose-limiting toxicities observed. Therefore, the 400 mg dose of LBL-007 was established as the RP2D and administered to 70 patients in phase II. Nine (11.3%) of 80 patients had grade 3 or 4 treatment-related adverse events, the most common of which included anemia (2.5%), hyponatremia (2.5%), increased alanine aminotransferase (2.5%), increased aspartate aminotransferase (1.3%), and fatigue (1.3%). Eight patients (10.0%) had treatment-related serious adverse events. No treatment-related deaths were reported. In immunotherapy-naive NPC patients (n = 12), ORR was 33.3%, disease control rate (DCR) was 75%, and median progression-free survival (PFS) was 10.8 months (95% CI, 1.3 to not estimated). In IO-treated NPC patients (n = 17), ORR was 11.8%, DCR was 64.7%, and median PFS was 2.7 months (95% CI, 1.4 to 4.9). For other tumors, ORRs were 15.8% in immunotherapy-naive patients and 3.7% in immunotherapy-treated patients. Patients with ≥ 2 + LAG-3 expression had a higher ORR of 28.0%, compared to 7.7% in those with < 2 + LAG-3 expression. Conclusion LBL-007 plus toripalimab exhibited a manageable safety profile in patients with advanced solid tumors and demonstrated promising antitumor activity in NPC, especially in immunotherapy-naive patients. These findings warrant further validation in future studies.https://doi.org/10.1186/s13045-025-01666-6 |
| spellingShingle | Gang Chen Dong-Chen Sun Yi Ba Ya-Xiong Zhang Ting Zhou Yuan-Yuan Zhao Hong-Yun Zhao Wen-Feng Fang Yan Huang Zhen Wang Chao Deng De-Sheng Hu Wei Wang Jin-Guan Lin Gui-Ling Li Su-Xia Luo Zhi-Chao Fu Hai-Sheng Zhu Hui-Li Wang Sheng-Li Cai Xiao-Qiang Kang Li Zhang Yun-Peng Yang Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial Journal of Hematology & Oncology |
| title | Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial |
| title_full | Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial |
| title_fullStr | Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial |
| title_full_unstemmed | Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial |
| title_short | Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial |
| title_sort | anti lag 3 antibody lbl 007 plus anti pd 1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors an open label multicenter phase ib ii trial |
| url | https://doi.org/10.1186/s13045-025-01666-6 |
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