An Anti-Bcma CAR T-Cell Therapy (C-CAR088) Shows Promising Safety and Efficacy Profile in Relapsed or Refractory Multiple Myeloma
Gang An, Weiwei Sui, Tingyu Wang, Xiaoyan Qu, Xian Zhang, Junfang Yang, Yan Zhang, Lu Zhang, Judy Zhu, Chengxiao Zheng, Xiuxiu Yan, Xiaoteng Lv, Liping Lan, Dingzhu Yang, Ningning Huo, Ting Han, Dijun Zhao, Shichao Qin, Junfeng Wu, Xin Yao, Shigui Zhu, Jiaqiang Ren, Li Zhang, Jiaqi Huang, Michael Humphries, Yihong Yao, Daobin Zhou, Jianyong Li, Peihua Lu
Abstract
Background: C-CAR088, an anti-BCMA CAR T-cell therapy is a novel 2nd generation 4-1BB chimeric antigen receptor T (CAR-T) cell therapy targeting BCMA which is specifically and highly expressed on multiple myeloma (MM) cells. C-CAR088 is manufactured in a serum-free, automated and digital, closed system. Initial, early clinical trial results in patients with R/R MM supported preclinical findings and showed promising efficacy and manageable safety profile (Yao, Blood (2019) 134 (Supplement_1): 50.) Methods: The dose escalation and expansion studies have been conducted at four medical centers in China to evaluate the safety and efficacy of C-CAR088 in patients with R/R MM who were previously treated with at least 2 lines of therapy including proteasome inhibitors (PIs) and IMiDs. C-CAR088 is administered to patients as a single intravenous dose after a standard 3-day cyclophosphamide/fludarabine conditioning regimen. Results: As of July 15, 2020, 24 patients were infused and 21 patients had evaluable data for safety and clinical response at dose levels of 1.0 x 106 CAR-T cells/kg (n=3), 3 x106 CAR-T cells/kg (n=11) and 4.5~6x106 CAR-T cells/kg (n=7). The median vein to vein time was 16 days. The manufacturing success rate was 100%. The median age of patients dosed was 60 years (range: 45-74 years).The median number of prior lines of therapy was 4 (range: 2-12 prior therapies). There were 17 (81%) patients with at least one and 12 (57.1%) patients with at least two high risk cytogenetic tumor changes. Five patients (23.8%) had bridging therapy. C-CAR088 treatment was well tolerated. 20 of 21 (95%) patients had Grade 1-2 CRS and one patient experienced Grade 3 CRS. Median time to CRS was 6.5 days (range: 1-11 days) and median duration of CRS was 5 days (range: 2-10 days). Four patients (19%) received tocilizumab for CRS treatment. Only one patient experienced a Grade 1 neurotoxicity event. No dose-limiting toxicities were observed and all adverse events were reversible. The best overall response (BOR) included 6 complete responses (CRs), 10 very good partial responses (VGPRs) and 4 partial responses (PRs). Median follow-up was 182 days (range: 30-375 days). The median duration of response has not been reached. In the 3 x106 CAR-T cells/kg dose group, 5/11(45%) patients achieved a CR. The C-CAR088 PK profile in peripheral blood showed a trend of a dose dependent profile. AUC0~28day and Cmax increased and Tmax decreased with dose (P<0.05). Conclusion: The clinical trial results in patients with R/R MM treated with C-CAR088 show a favorable safety profile and promising signs of efficacy. We will continue to evaluate these patients to understand the long-term effect of C-CAR088 in multiple myeloma patients. Clinical trial information: NCT04322292、NCT03815383、NCT03751293、NCT04295018 Research Sponsor: Cellular Biomedicine Group, Inc. Disclosures Zhu: Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Zheng:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Yan:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Lv:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Lan:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Yang:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Huo:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Han:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Zhao:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Qin:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Wu:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Yao:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Zhu:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Ren:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Zhang:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Huang:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Humphries:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Yao:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company.