Xu Yang, Zhang Xuzhao, Xin Dijia, Zhang Jiawei, Wang Luyao, Fan Yili, Chen Boxiao, Lei Wen, Qiu Xi, Jiang Huawei, Xiao Xibin, Huang Liansheng, Yu Jiandong, Yang Xin, Yang Wenjun, Zhu Jiangao, Qian Wenbin
Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Carbiogene Therapeutics Ltd., Hangzhou, China.
Cancer Immunol Res. 2025 Jan 9;13(1):23-34. doi: 10.1158/2326-6066.CIR-24-0051.
B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM); however, whether patients have long-term responses has yet to be established. We investigated the feasibility of CBG-002, a CD27-armored BCMA CAR T-cell therapy, to improve clinical efficacy in patients with RRMM. We present preclinical data showing the activity of CBG-002 against myeloma and results from a phase I clinical trial (NCT04706936) evaluating its safety and efficacy in patients with RRMM. The primary endpoint was safety, as assessed by grade 3 or 4 adverse events (AE). Key secondary endpoints were overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). A total of 11 patients were enrolled and received CBG-002 therapy. Nine patients developed grade 1 or 2 cytokine release syndrome (CRS), whereas no patients experienced grade 3 or higher CRS or immune effector cell-associated neurotoxicity syndrome. Other grade 3 or higher AEs included neutropenia (72.7%), thrombocytopenia (45.5%), and anemia (36.4%). At a median follow-up of 16.7 months, the ORR was 81.8%, including a stringent complete response/complete response rate of 45.5%, very good partial response rate of 18.2%, and partial response rate of 18.2%, with a median DOR of 8.9 (range 1.8-21.9) months. The median OS was not reached, and the median PFS was 8.5 (2.7-22.9) months. In this phase I study, CBG-002, a CD27-armored BCMA CAR T-cell therapy, demonstrated safety and clinical efficacy in patients with RRMM.
B细胞成熟抗原（BCMA）嵌合抗原受体（CAR）T细胞疗法已被批准用于治疗复发难治性多发性骨髓瘤（RRMM）；然而，患者是否能获得长期缓解尚未明确。我们研究了CD27强化的BCMA CAR T细胞疗法CBG - 002在改善RRMM患者临床疗效方面的可行性。我们展示了CBG - 002抗骨髓瘤活性的临床前数据以及一项评估其在RRMM患者中安全性和疗效的I期临床试验（NCT04706936）的结果。主要终点是安全性，通过3级或4级不良事件（AE）进行评估。关键次要终点是总缓解率（ORR）、缓解持续时间（DOR）、无进展生存期（PFS）和总生存期（OS）。共有11名患者入组并接受了CBG - 002治疗。9名患者出现1级或2级细胞因子释放综合征（CRS），而没有患者出现3级或更高等级的CRS或免疫效应细胞相关神经毒性综合征。其他3级或更高等级的AE包括中性粒细胞减少（72.7%）、血小板减少（45.5%）和贫血（36.4%）。在中位随访16.7个月时，ORR为81.8%，包括严格完全缓解/完全缓解率为45.5%、非常好的部分缓解率为18.2%和部分缓解率为18.2%，中位DOR为8.9（范围1.8 - 21.9）个月。中位OS未达到，中位PFS为8.5（2.7 - 22.9）个月。在这项I期研究中，CD27强化的BCMA CAR T细胞疗法CBG - 002在RRMM患者中显示出安全性和临床疗效。
