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1396 Results from Lummicar-1: A Phase 1 Study of Fully Human B-Cell Maturation Antigen-Specific CAR T Cells (CT053) in Chinese Subjects with Relapsed and/or Refractory Multiple Myeloma

Program: Oral and Poster Abstracts
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster I
Hematology Disease Topics & Pathways:
Biological, multiple myeloma, Diseases, Therapies, CAR-Ts, Plasma Cell Disorders, Lymphoid Malignancies, Clinically relevant
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Wenming Chen, MD, PhD1*, Chengcheng Fu, MD, PhD2*, Zhen Cai, MD, PhD3*, Zonghai Li, MD, PhD4*, Huijuan Wang, MD, PhD5*, Lingzhi Yan, MD, PhD6*, Yin Wu, MD, PhD7*, Xiaolan Shi, MD, PhD6*, Wen Gao, MD8, Shuang Yan, MD6*, Wei Wang, MD, PhD4*, Xiaoyan Han, MD, PhD9*, Gaofeng Zheng, MD, PhD10*, Yanling Wen, MD10*, Jun Xiao, MD4*, Huamao Wang, PhD11* and Hong Ma, MD12

1Department of Hematology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
2Department of Hematology / Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
3Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
4CARsgen Therapeutics Co. Ltd, Shanghai, China
5Beijing Chao-Yang Hospital, Capital medical University, Beijing, China
6National Clinical Research Center for Hematologic Diseases, Suzhou, Suzhou, China
7Department of Hematology, Beijing Chao-Yang Hospital of Capital Medical University, Beijing, China
8Beijing Chaoyang Hospital, Capital medical University, BEIJING, China
9Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
10The First Affiliated Hospital, School of medicine, Zhejiang University, Hangzhou, China
11CARsgen Therapeutics Co. LtD, Shanghai, China
12CARsgen Therapeutics Corporation, Bellaire, TX

Background: CT053 are autologous T cells genetically modified with a second-generation chimeric antigen receptor (CAR) incorporating a fully human B-cell maturation antigen (BCMA)-specific single-chain fragment variant (25C2) with high binding affinity. Twenty-four subjects were previously treated in investigator-initiated (IIT) studies with 87.5% overall response rate (ORR), 79.2% complete response (CR) and a median duration of response of 21.8 months without inducing immunogenicity [Blood (2019) 134 (Supplement_1): 4435]. We report herein the first disclosed results from the ongoing phase 1 study (LUMMICAR-1) in China (NCT03975907).

Methods: The phase 1 study included subjects with relapsed/refractory multiple myeloma (RRMM) who had received ≥3 prior therapy regimens including a proteasome inhibitor and an immunomodulatory drug, and had measurable disease per 2016 International Myeloma Working Group (IMWG) criteria. All subjects received conditioning treatment of cyclophosphamide (300 mg/m2/day ×3 days) and fludarabine (25 mg/m2/ day × 3 days). After conditioning, subjects received a single infusion of CT053 at the 1.0-1.5×108 CAR+ T-cell dose. Primary objectives for phase 1 were to evaluate the safety and tolerability of CT053 and to identify the recommended phase 2 dose. Adverse events (AEs) were graded using CTCAE, v5.0; cytokine release syndrome (CRS) and neurotoxicity were graded according to ASTCT CRS consensus grading system (Lee DW et al, 2019). Response was assessed per 2016 IMWG criteria.

Results: As of July 20, 2020, a total of 14 subjects have been enrolled in the study. All 14 subjects have been apheresed and received CT053 infusion, including 3 subjects who received 1.0×108 CAR+ T cells and 3 subjects who received 1.5×108 CAR+ T cells at dose escalation, followed by 8 subjects who received 1.5×108 CAR+ T cells at dose expansion. The 14 batches of CT053 were manufactured in a median of 8 days (range 7-10). Treated subjects had a median age of 54 years (range 34-62) and had received a median of 6 (range 3-7) prior lines of therapy. Of the 14 subjects, 10 (71.4%) received autologous stem cell transplantation, 2 (14.2%) had extramedullary disease at baseline, and 5 (35.7%) had high-risk cytogenetics. No subject received bridging therapy. At data cutoff, 12 subjects had at least 4 weeks of safety and efficacy assessment with median follow-up of 5 months (range, 1-11).

No dose-limiting toxicities were detected. The most common ≥ grade 3 AE was hematological toxicity. Of the 12 subjects with at least 4 weeks follow-up, all experienced ≥ grade 3 neutropenia (100%), 91.7% of subjects had ≥ grade 3 thrombocytopenia, and most recovered to ≤ grade 2 within 2 weeks. No grade 3 or higher CRS or neurotoxicity was observed. Eleven of 12 subjects (91.7%) experienced grade 1 or 2 CRS, including 3 subjects who experienced grade 2 CRS and 8 subjects who experienced grade 1 CRS. CRS events occurred at a median of 6 days (range 2-12) post-infusion with a median duration of 7 days, following a generally predicable onset pattern. Eight subjects received tocilizumab treatment, of whom one subject with grade 2 CRS received both tocilizumab and steroid.

At the data cutoff, among 12 subjects with at least 4 weeks of efficacy assessment, a 100% ORR was observed, with 4 stringent complete responses (sCR), 1 CR, 3 very good partial responses and 4 partial responses. All 5 subjects with CR/sCR were minimal residual disease (MRD)-negative at the 10 5 sensitivity level. Responses were independent of baseline BCMA expression in bone marrow.

CT053 transgene levels showed expansion and persistence in peripheral blood, with peak expansion at 7-14 days after dosing in all subjects, with peak copies 45,469 (range 11,825-258,574). Serum C-reactive protein and cytokine levels (i.e., IL-6, IFNγ, IL-8, IL-10) increased post-infusion within 7 days and correlated with the onset of CRS symptoms. No immunogenicity was detected.

Conclusion: These results demonstrate that CT053 at a target dose of 1.0-1.5×108 CAR+ T cells delivers early and deep responses, including MRD negativity in all complete responders, with an acceptable safety profile in subjects with heavily pretreated RRMM. The results from this LUMMICAR-1 study are consistent with the previous IIT phase 1 studies and the ongoing North American LUMMICAR-2 study and support the launch of pivotal LUMMICAR-1 study in China. Updated results will be presented at this conference.

Disclosures: Li: CARsgen Therapeutics Co. LtD: Current Employment, Current equity holder in private company. Wang: CARsgen Therapeutics Corp.: Current Employment. Xiao: CARsgen Therapeutics Corp.: Current Employment. Wang: CARsgen Therapeutics Co. LtD: Current Employment, Current equity holder in private company. Ma: CARsgen Therapeutics Corp.: Current Employment.

*signifies non-member of ASH