Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma
Background Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy showed remarkable efficacy in patients with relapsed or refractory multiple myeloma (RRMM). This phase 1 dose-escalation and expansion study developed C-CAR088, a novel second-generation humanized anti-...
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BMJ Publishing Group
2022-09-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/9/e005145.full |
| _version_ | 1827207588449615872 |
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| author | Yan Zhang Lu Zhang Xian Zhang Xin Yao Tingyu Wang Dan Zhu Liping Lan Peihua Lu Yihong Yao Lugui Qiu Xiaoyan Qu Gang An Weiwei Sui Junfang Yang Jiaqi Huang Shigui Zhu Chengxiao Zheng Kevin Zhu Yutian Wei Xiaoteng Lv Daobin Zhou Jianyong Li |
| author_facet | Yan Zhang Lu Zhang Xian Zhang Xin Yao Tingyu Wang Dan Zhu Liping Lan Peihua Lu Yihong Yao Lugui Qiu Xiaoyan Qu Gang An Weiwei Sui Junfang Yang Jiaqi Huang Shigui Zhu Chengxiao Zheng Kevin Zhu Yutian Wei Xiaoteng Lv Daobin Zhou Jianyong Li |
| author_sort | Yan Zhang |
| collection | DOAJ |
| description | Background Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy showed remarkable efficacy in patients with relapsed or refractory multiple myeloma (RRMM). This phase 1 dose-escalation and expansion study developed C-CAR088, a novel second-generation humanized anti-BCMA CAR T-cell therapy, and assessed the safety and efficacy of three dosages of C-CAR088 in patients with RRMM.Methods Patients received lymphodepletion with three doses of cyclophosphamide (300 mg/m2) and three doses of fludarabine (30 mg/m2) on days –5, –4, and –3, followed by an infusion of C-CAR088 on day 0. Doses of 1.0×106, 3.0×106, and 6.0×106 CAR T cells/kg (±20%) were tested in the dose-escalation cohorts and expansion cohorts. The primary endpoint was treatment safety, including the rate of treatment-emergent adverse events after cell infusion. Secondary endpoints were the overall response rate and progression-free survival. The exploratory endpoints were the quantification of C-CAR088 CAR T cells, selection of cytokines and chemokines in blood, and measurement of tumor BCMA expression.Results As of July 2, 2021, 31 patients had been infused with C-CAR088. Any grade cytokine release syndrome (CRS) occurred in 29 patients (93.5%), and grade 3 CRS occurred in 3 patients (9.7%). One patient from the high-dose group (4.5–6.0×106 CAR T cells/kg) developed grade 1 neurotoxicity. No dose-limiting toxicities were observed in any dose group, and all adverse events were reversible after proper management. The overall response, stringent complete response, complete response (CR), and very good partial response rates were 96.4%, 46.4%, 10.7%, and 32.1%, respectively. The CR rate in the medium-dose (3.0×106 CAR T cells/kg) and high-dose (4.5–6.0×106 CAR T cells/kg) groups was 54.5% and 71.4%, respectively. In the CR group, 15 (93.7%) patients achieved minimal residual disease (MRD) negativity (test sensitivity >1/10−5). All seven patients with double-hit or triple-hit multiple myeloma achieved MRD-negative CR.Conclusions The present study demonstrated that C-CAR088 had a good safety profile and high antitumor activity in patients with RRMM, constituting a promising treatment option for RRMM.Trial registration number NCT03815383, NCT03751293, NCT04295018, and NCT04322292. |
| first_indexed | 2024-04-11T16:39:14Z |
| format | Article |
| id | doaj.art-68b5531b55cd4978b5a00d2f1fdf0450 |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2025-03-21T12:42:27Z |
| publishDate | 2022-09-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-68b5531b55cd4978b5a00d2f1fdf04502024-06-27T09:55:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-09-0110910.1136/jitc-2022-005145Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myelomaYan Zhang0Lu Zhang1Xian Zhang2Xin Yao3Tingyu Wang4Dan Zhu5Liping Lan6Peihua Lu7Yihong Yao8Lugui Qiu9Xiaoyan Qu10Gang An11Weiwei Sui12Junfang Yang13Jiaqi Huang14Shigui Zhu15Chengxiao Zheng16Kevin Zhu17Yutian Wei18Xiaoteng Lv19Daobin Zhou20Jianyong Li211 Center for Single-Cell Omics and Health, School of Public Health, Xi`an Jiaotong University Health Science Center, Xi`an, Shaanxi, ChinaDepartment of hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China3 Department of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan, ChinaCellular Biomedicine Group Inc, Shanghai, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China2Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, nanchong, ChinaCellular Biomedicine Group Inc, Shanghai, ChinaDepartment of Medical Oncology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, ChinaCellular Biomedicine Group Inc, Shanghai, China2 Tianjin Institutes of Health Science, Tianjin, ChinaDepartment of Hematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China1 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaDepartment of hematology, Hebei Yanda Lu Daopei Hospital, Langfang, ChinaCellular Biomedicine Group Inc, Shanghai, ChinaCellular Biomedicine Group Inc, Shanghai, ChinaCellular Biomedicine Group Inc, Shanghai, ChinaUniversity of Maryland School of Medicine, Baltimore, Maryland, USACellular Biomedicine Group Inc, Shanghai, ChinaCellular Biomedicine Group Inc, Shanghai, ChinaDepartment of hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaDepartment of Cardioloqy, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, ChinaBackground Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy showed remarkable efficacy in patients with relapsed or refractory multiple myeloma (RRMM). This phase 1 dose-escalation and expansion study developed C-CAR088, a novel second-generation humanized anti-BCMA CAR T-cell therapy, and assessed the safety and efficacy of three dosages of C-CAR088 in patients with RRMM.Methods Patients received lymphodepletion with three doses of cyclophosphamide (300 mg/m2) and three doses of fludarabine (30 mg/m2) on days –5, –4, and –3, followed by an infusion of C-CAR088 on day 0. Doses of 1.0×106, 3.0×106, and 6.0×106 CAR T cells/kg (±20%) were tested in the dose-escalation cohorts and expansion cohorts. The primary endpoint was treatment safety, including the rate of treatment-emergent adverse events after cell infusion. Secondary endpoints were the overall response rate and progression-free survival. The exploratory endpoints were the quantification of C-CAR088 CAR T cells, selection of cytokines and chemokines in blood, and measurement of tumor BCMA expression.Results As of July 2, 2021, 31 patients had been infused with C-CAR088. Any grade cytokine release syndrome (CRS) occurred in 29 patients (93.5%), and grade 3 CRS occurred in 3 patients (9.7%). One patient from the high-dose group (4.5–6.0×106 CAR T cells/kg) developed grade 1 neurotoxicity. No dose-limiting toxicities were observed in any dose group, and all adverse events were reversible after proper management. The overall response, stringent complete response, complete response (CR), and very good partial response rates were 96.4%, 46.4%, 10.7%, and 32.1%, respectively. The CR rate in the medium-dose (3.0×106 CAR T cells/kg) and high-dose (4.5–6.0×106 CAR T cells/kg) groups was 54.5% and 71.4%, respectively. In the CR group, 15 (93.7%) patients achieved minimal residual disease (MRD) negativity (test sensitivity >1/10−5). All seven patients with double-hit or triple-hit multiple myeloma achieved MRD-negative CR.Conclusions The present study demonstrated that C-CAR088 had a good safety profile and high antitumor activity in patients with RRMM, constituting a promising treatment option for RRMM.Trial registration number NCT03815383, NCT03751293, NCT04295018, and NCT04322292.https://jitc.bmj.com/content/10/9/e005145.full |
| spellingShingle | Yan Zhang Lu Zhang Xian Zhang Xin Yao Tingyu Wang Dan Zhu Liping Lan Peihua Lu Yihong Yao Lugui Qiu Xiaoyan Qu Gang An Weiwei Sui Junfang Yang Jiaqi Huang Shigui Zhu Chengxiao Zheng Kevin Zhu Yutian Wei Xiaoteng Lv Daobin Zhou Jianyong Li Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma Journal for ImmunoTherapy of Cancer |
| title | Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma |
| title_full | Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma |
| title_fullStr | Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma |
| title_full_unstemmed | Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma |
| title_short | Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma |
| title_sort | phase 1 study of c car088 a novel humanized anti bcma car t cell therapy in relapsed refractory multiple myeloma |
| url | https://jitc.bmj.com/content/10/9/e005145.full |
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