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547 A Phase 1/2 Study of a Novel Fully Human B-Cell Maturation Antigen-Specific CAR T Cells (CT103A) in Patients with Relapsed and/or Refractory Multiple Myeloma

Program: Oral and Poster Abstracts
Type: Oral
Session: 704. Cellular Immunotherapies: Cellular Therapies for Myeloma
Hematology Disease Topics & Pathways:
Clinical Trials, Workforce
Sunday, December 12, 2021: 4:30 PM

Chunrui Li, MD, PhD1, Di Wang, MD, PhD2*, Yongping Song3*, Jianyong Li4, He Huang5,6, Bing Chen7*, Jing Liu8*, Kai Hu9*, Hanyun Ren, MD10, Xi Zhang11*, Zhenyu Li, MD12*, Dehui Zou13*, Qingsong Yin14*, Lijuan Chen, MD, PhD15*, Yongxian HU, MD16*, Yong Xu, PhD17*, Qian Cheng18*, Yuelu Guo19*, Yujun Dong, MD10*, Li Gao20,21*, Aining Xu22*, Songbai Cai23*, Wen Wang24*, Ming Wu23*, Jue Wang, MD, PhD25*, Liting Chen26*, Jianfeng Zhou1* and Lugui Qiu13

1Department of Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
3Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
4Department of Hematology, Pukou CLL Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
5Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Institute of Hematology, Zhejiang University, Hangzhou, China
7Department of Hematology, Nanjing University Medical School , the Affiliated Nanjing Drum Tower Hospital, NanJing, China
8Department of Hematology, The Third Xiangya Hospital of Central South University, Hunan, China
9Department of Hematology, Beijing Boren Hospital, Beijing, China
10Department of Hematology, Peking University First Hospital, Beijing, China
11Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, China
12Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
13State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Blood Diseases Hospital & Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
14the Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Zhengzhou, China
15Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
16Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, AL, China
17Department of Hematology, Nanjing University Medical School, the Affiliated Nanjing Drum Tower Hospital, Nanjing, China
18Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha, China
19Beijing Boren Hospital, Beijing, AK, China
20Department of Hematology, Xinqiao Hospital, Army medical University, Chongqing, China
21The Second Affiliated Hospital of Army Medical University, Chongqing, China
22Nanjing IASO Biotherapeutics Ltd, Nanjing, Jiangsu, Nanjing, China
23Nanjing IASO Biotherapeutics Ltd, Shanghai, China
24Nanjing IASO Biotherapeutics Ltd, Nanjing, CHN
25Department of Hematology,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
26Department of Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Science, Wuhan, China

Background CT103A, a fully human BCMA-specific chimeric antigen receptor (CAR) T-cell therapy product showed excellent safety and promising efficacy in heavily pretreated relapsed and refractory multiple myeloma (RRMM) patients in our previous report [Blood. 2021; 137 (21): 2890-2901]. The unique CAR structure containing fully human single-chain variable fragments (scFvs) may bypass the potential host anti-CAR immunogenicity and retain antitumor activity. Here we reported the safety and efficacy results of 71 patients in 1.0×106 CAR+ T cells/kg cohort from the ongoing phase1/2 study (ChiCTR1800018137/ ChiCTR2000033946). Notably, it was the first time that prior BCMA CAR-T exposed patients were eligible to participate in an anti-BCMA CAR-T cell trial.

Methods This phase 1/2 study of CT103A is single-arm designed and is conducted in 13 centers in China. The study enrolled RRMM patients who had received ≥ 3 lines of prior therapies containing at least a proteasome inhibitor and an immunomodulatory agent and were refractory to their last line of treatment. 1.0 × 106 CAR+ T cells/Kg was previously identified as recommended phase 2 dose (RP2D). Lymphodepletion with fludarabine and cyclophosphamide was performed for three consecutive days. After 1-day rest, patients received CT103A. The primary objectives of this study were to assess the safety and efficacy of CT103A at RP2D. The cellular pharmacokinetic profile of CT103A in peripheral blood was investigated by measuring CAR transgene levels using droplet digital polymerase chain reaction (ddPCR) and CAR-T cells by flow cytometry. Minimal residual disease (MRD) negativity was evaluated in bone marrow aspirate by standardized Euroflow 8-color flow cytometry with a minimum sensitivity of 10-5 nucleated cells. Immunogenicity was assessed by MSD-based antidrug antibody (ADA) assay.

Results: As of the July 15, 2021, 71 patients [59.2% male; median age 58.0 years (range 41-71)] with RRMM received CT103A (9 in phase 1a; 17 in phase 1b; 45 in phase 2). The median follow-up time was 147 days (range 31 to 1029). The treated patients had received a median of 4 (range 3-13) lines of prior therapy. 28.2% and 18.3% were previously treated with auto-HSCT and anti-CD38 antibody respectively. Notably, 18.3% had previously received CAR-T therapy. What’s more, 7% of the patients had the extramedullary disease at baseline, and 76.1% had high-risk cytogenetics.

The most common ≥ grade 3 treatment-related AEs were hematological toxicities. 93.0% of the patients experienced CRS, among which only 2.8% were grade 3. All CRS cases were rapidly relieved after conventional CRS intervention, including tocilizumab and steroids. The median time to CRS onset was 6 days (range 1-12) with a median duration of 4 days (range 1-27). Only one (1.4%) patient experienced grade 2 ICANS which manifested as a transiently decreased level of consciousness and soon recovered without intervention.

All 71 patients were evaluable for at least one month of efficacy assessment. The median time to first response was 15 days (range 11-124). A 94.4% ORR was observed, with 50.7% ≥ CR, 26.8% VGPR, and 16.9% PR. Among them, 50 patients who have completed follow-up of 3 months achieved 96.0% ORR, with 54.0% ≥ CR, 28% VGPR, and 14% PR. For 13 patients who have previously been treated with CAR-T therapy, ORR was 76.9%, with ≥ CR rate of 38.5%,VGPR of 15.4%, and PR of 23.1%. Of the 69 patients with evaluable bone marrow aspirate, 92.8% achieved MRD-negativity with a median time to MRD-negative of 17 days (range 13-180), and among them, 75.0% (95%CI 53.1-87.6%) achieved sustained MRD negativity over six months.

The expansion of CT103A reached the peak at a median of 12 days (range 5 to 29). CT103A was still detectable in 88.5% (23/26) patients at 6 months and 87.5% (14/16) patients at 12 months after infusion. The first enrolled patient remains in sCR for 34 months with significant persistence of CT103A transgene. In addition, only 2 of 71 patients were detected positive for anti-drug antibody, which was reported to be a high-risk factor for disease relapse/progression after CAR-T therapy.

Conclusion: The impressive efficacy of CT103A, including time to response, overall response rate, and durability, was corroborated by robust expansion and prolonged persistence of CT103A. The expansion and clinical benefits of CT103A did not seem to be influenced by prior murine BCMA CAR-T.

Disclosures: No relevant conflicts of interest to declare.

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