Safety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II study
Abstract Background Pucotenlimab is a novel recombinant humanized anti-PD-1 (Programmed death-1) monoclonal antibody, which belongs to the human IgG4/kappa subtype, and can selectively block the binding of PD-1 with its ligands PD-L1 and PD-L2. Methods In this phase 2 trial, patients with locally ad...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-10473-y |
| _version_ | 1811165855965249536 |
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| author | Chuanliang Cui Yu Chen Zhiguo Luo Zhengyun Zou Yu Jiang Hongming Pan Qingxia Fan Jianfu Zhao Qing Xu Renbing Jiang Xuan Wang Taiyang Ma Zhen Guo Lu Si Zhihong Chi Xinan Sheng Yiwei Dou Qian Tan Di Wu Jun Guo |
| author_facet | Chuanliang Cui Yu Chen Zhiguo Luo Zhengyun Zou Yu Jiang Hongming Pan Qingxia Fan Jianfu Zhao Qing Xu Renbing Jiang Xuan Wang Taiyang Ma Zhen Guo Lu Si Zhihong Chi Xinan Sheng Yiwei Dou Qian Tan Di Wu Jun Guo |
| author_sort | Chuanliang Cui |
| collection | DOAJ |
| description | Abstract Background Pucotenlimab is a novel recombinant humanized anti-PD-1 (Programmed death-1) monoclonal antibody, which belongs to the human IgG4/kappa subtype, and can selectively block the binding of PD-1 with its ligands PD-L1 and PD-L2. Methods In this phase 2 trial, patients with locally advanced or metastatic melanoma who had failed conventional treatment (chemotherapy, targeted therapy, interferon, IL-2, et al.) were recruited. The patients were administrated with Pucotenlimab of 3 mg/kg every 3 weeks until disease progression, intolerable toxicity, or treatment discontinuation for any other reasons. The primary endpoint was the overall response rate (ORR). The secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. Results One-hundred and nineteen patients were enrolled and followed up for 19.32 (ranging from 15.901 to 24.608) months by the cutoff date of July 30th, 2021. The ORR was 20.17% (24/119, 95% CI, 13.370%-28.506%) based on both independent review committee (IRC) and the investigator’s assessment per RECIST v1.1. The median PFS were 2.89 (95% CI, 2.037–4.074) months and 2.46 (95% CI, 2.004–4.008) months based on IRC and investigator’s assessment, respectively, per RECIST v1.1. The median OS was 16.59 (95% CI, 13.963–26.973) months. Treatment-related adverse events (TRAEs) occurred in 77.3% (92/119) of the patients. The incidence of Grade ≥ 3 TRAEs was 15.1% (18/119). In addition, none of the patients died because of TRAEs. As for biomarker analysis, Eotaxin (CCL11) and MCP-1 (CCL2) were related to treatment response, while TNF-α and VEGF were related to treatment failure. Conclusions Pucotenlimab as a ≥ 2nd line therapy showed promising efficacy and tolerable toxicity for patients with locally advanced or metastatic melanoma. Trial registration Clinicaltrials.gov Identifier: NCT04749485 (registered retrospectively on 11/02/2021). |
| first_indexed | 2024-04-10T15:44:18Z |
| format | Article |
| id | doaj.art-83c21142fb064ae8ae697bb5f09ec8bc |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-10T15:44:18Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj.art-83c21142fb064ae8ae697bb5f09ec8bc2023-02-12T12:14:43ZengBMCBMC Cancer1471-24072023-02-0123111110.1186/s12885-022-10473-ySafety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II studyChuanliang Cui0Yu Chen1Zhiguo Luo2Zhengyun Zou3Yu Jiang4Hongming Pan5Qingxia Fan6Jianfu Zhao7Qing Xu8Renbing Jiang9Xuan Wang10Taiyang Ma11Zhen Guo12Lu Si13Zhihong Chi14Xinan Sheng15Yiwei Dou16Qian Tan17Di Wu18Jun Guo19Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & InstituteFujian Cancer HospitalFudan University Shanghai Cancer CenterDrum Tower Hospital, Affiliated to Medical School of Nanjing UniversityWest China Hospital, Sichuan UniversityZhejiang University School of Medicine Sir Run Run Shaw HospitalThe First Affiliated Hospital of Zhengzhou UniversityThe First Affiliated Hospital of Jinan UniversityShanghai Tenth People’s HospitalThe Affiliated Cancer Hospital of Xinjiang Medical UniversityKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & InstituteTaizhou Hanzhong Biomedical Co., Ltd. (A Member of Lepu Biopharma Co., Ltd.)The First Hospital of Jilin UniversityKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & InstituteTaizhou Hanzhong Biomedical Co., Ltd. (A Member of Lepu Biopharma Co., Ltd.)Taizhou Hanzhong Biomedical Co., Ltd. (A Member of Lepu Biopharma Co., Ltd.)The First Hospital of Jilin UniversityKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & InstituteAbstract Background Pucotenlimab is a novel recombinant humanized anti-PD-1 (Programmed death-1) monoclonal antibody, which belongs to the human IgG4/kappa subtype, and can selectively block the binding of PD-1 with its ligands PD-L1 and PD-L2. Methods In this phase 2 trial, patients with locally advanced or metastatic melanoma who had failed conventional treatment (chemotherapy, targeted therapy, interferon, IL-2, et al.) were recruited. The patients were administrated with Pucotenlimab of 3 mg/kg every 3 weeks until disease progression, intolerable toxicity, or treatment discontinuation for any other reasons. The primary endpoint was the overall response rate (ORR). The secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. Results One-hundred and nineteen patients were enrolled and followed up for 19.32 (ranging from 15.901 to 24.608) months by the cutoff date of July 30th, 2021. The ORR was 20.17% (24/119, 95% CI, 13.370%-28.506%) based on both independent review committee (IRC) and the investigator’s assessment per RECIST v1.1. The median PFS were 2.89 (95% CI, 2.037–4.074) months and 2.46 (95% CI, 2.004–4.008) months based on IRC and investigator’s assessment, respectively, per RECIST v1.1. The median OS was 16.59 (95% CI, 13.963–26.973) months. Treatment-related adverse events (TRAEs) occurred in 77.3% (92/119) of the patients. The incidence of Grade ≥ 3 TRAEs was 15.1% (18/119). In addition, none of the patients died because of TRAEs. As for biomarker analysis, Eotaxin (CCL11) and MCP-1 (CCL2) were related to treatment response, while TNF-α and VEGF were related to treatment failure. Conclusions Pucotenlimab as a ≥ 2nd line therapy showed promising efficacy and tolerable toxicity for patients with locally advanced or metastatic melanoma. Trial registration Clinicaltrials.gov Identifier: NCT04749485 (registered retrospectively on 11/02/2021).https://doi.org/10.1186/s12885-022-10473-yPD-1Monoclonal antibodyPucotenlimabHX008Melanoma |
| spellingShingle | Chuanliang Cui Yu Chen Zhiguo Luo Zhengyun Zou Yu Jiang Hongming Pan Qingxia Fan Jianfu Zhao Qing Xu Renbing Jiang Xuan Wang Taiyang Ma Zhen Guo Lu Si Zhihong Chi Xinan Sheng Yiwei Dou Qian Tan Di Wu Jun Guo Safety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II study BMC Cancer PD-1 Monoclonal antibody Pucotenlimab HX008 Melanoma |
| title | Safety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II study |
| title_full | Safety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II study |
| title_fullStr | Safety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II study |
| title_full_unstemmed | Safety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II study |
| title_short | Safety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II study |
| title_sort | safety and efficacy of pucotenlimab hx008 a humanized immunoglobulin g4 monoclonal antibody in patients with locally advanced or metastatic melanoma a single arm multicenter phase ii study |
| topic | PD-1 Monoclonal antibody Pucotenlimab HX008 Melanoma |
| url | https://doi.org/10.1186/s12885-022-10473-y |
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