Remission observed from a phase 1 clinical study of CAR-T therapy with safety switch targeting BCMA for patients with relapsed/refractory multiple myeloma.

Authors

null

Yarong Liu

HRAIN Biotechnology, Shanghai, China

Yarong Liu , Zhi Chen , Runhong Wei , Lin Shi , Feng He , Zixiao Shi , Tao Jin , Ronglin Xie , Baofeng Wei , Jing Chen , Hongliang Fang , Bo Zhu , Qi-Jing Li , Pin Wang

Organizations

HRAIN Biotechnology, Shanghai, China, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China, Institute of Cancer, Xinqiao Hospital, Chongqing, China, Duke University Medical Center, Durham, NC, University of Southern California, Los Angeles, CA

Research Funding

Pharmaceutical/Biotech Company

Background: Encouraging results are seen from several early phase clinical trials on the cellular immunotherapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) targeting B cell maturation antigen (BCMA) for the treatment of relapsed/refractory (RR) multiple myeloma (MM). We developed an anti-BCMA CAR-T cell product manufactured via gamma-retrovirus-mediated transduction of activated T cells to express a second-generation CAR with the 4-1BB costimulatory domain along with a truncated epidermal growth factor receptor (tEGFR) as a safety switch. The preclinical study confirmed its high reactivity against MM cells. Methods: A phase 1 clinical trial (NCT03093168) has been launched to evaluate the safety and feasibility of this BCMA CAR-T cell product for treating RRMM. The enrolled RRMM patients had received at least 3 prior treatment regimens, including a proteasome inhibitor and an immunomodulatory agent, or are double-refractory, and have over 20% BCMA expression on plasma cells. Patients were subjected to a lymphodepleting regimen with Cy once (300 mg/m2, d-3) and Flu daily for 3 days (25 mg/m2, d-5 to d-3) prior to the CAR-T infusion (d0) at a dose of 9×106 CAR+ cells/kg. The efficacy was assessed by the International Uniform Response Criteria for Multiple Myeloma, and the toxicity iss graded by CTCAE 4.02. Results: As of December 31, 2017, 10 patients had been infused with this intended dose of the autologous BCMA CAR-T cells, and 7 patients had reached at least 1 month of follow-up. As of this data cut-off, no greater than Grade 1 neurotoxicities or cytokine release syndrome (CRS) had been observed. The overall response rate (ORR) for the 7 evaluable patients was 86%, including 2 sCRs and 2 MRD-negative responses (2 VGPR). The CAR-T cell expansion and persistence were consistently observed throughout these patients. Conclusions: Our result demonstrates the promising efficacy with the infused dose, including 2 sCRs and ongoing clinical responses for more than 12 months, with only mild and manageable CRS to date. These initial data provide strong evidence to support the further development of this anti-myeloma cellular immunotherapy. Clinical trial information: NCT03093168

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Abstract Details

Meeting

2018 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Hematologic Malignancies—Plasma Cell Dyscrasia

Track

Hematologic Malignancies—Plasma Cell Dyscrasia

Sub Track

Multiple Myeloma

Clinical Trial Registration Number

NCT03093168

Citation

J Clin Oncol 36, 2018 (suppl; abstr 8020)

DOI

10.1200/JCO.2018.36.15_suppl.8020

Abstract #

8020

Poster Bd #

29

Abstract Disclosures