Relmacabtagene autoleucel (relma‐cel) CD19 CAR‐T therapy for adults with heavily pretreated relapsed/refractory large B‐cell lymphoma in China

• Published in: Cancer medicine (Malden, MA) MA), 2021-02, Vol.10 (3), p.999-1011
• Main Authors: Ying, Zhitao, Yang, Haiyan, Guo, Ye, Li, Wenyu, Zou, Dehui, Zhou, Daobin, Wang, Zhao, Zhang, Mingzhi, Wu, Jianqiu, Liu, Hui, Zhang, Pian, Yang, Su, Zhou, Zisong, Zheng, Hongxia, Song, Yuqin, Zhu, Jun
• Format: Article
• Language: English
• Subjects: Adverse events; B-cell lymphoma; CAR‐T; CD19; CD19 antigen; cellular kinetics; Chemotherapy; Chimeric antigen receptors; Clinical Cancer Research; Clinical trials; Cryopreservation; Cyclophosphamide; Drug dosages; Fludarabine; Growth factors; Hypotheses; LBCL; Lymphocytes; Lymphoma; Neurotoxicity; Original Research; Patients; Pharmacokinetics; Relma‐cel; Response rates; Tumor necrosis factor-TNF
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.3686

Background Despite numerous chimeric antigen receptor T‐cell (CAR‐T) trials conducted in China, no CAR‐T has been registered in the country. Furthermore, China law and regulations restrict the export of patient material for CAR‐T manufacture abroad. Relma‐cel (JWCAR029), an anti‐CD19 product produced with a commercial‐ready process in China, was evaluated in the first prospective, single‐arm, multicenter, pivotal study of CAR‐T therapy conducted under Chinese IND to support an NMPA‐accepted BLA submission in relapsed/refractory (r/r) LBCL (NCT04089215). Methods Patients were randomized to receive either 100 × 106 (low dose, n = 27) or 150 × 106 (high dose, n = 32) CAR+ T‐cells as a single infusion following lymphodepleting chemotherapy (fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 daily × 3), and then, monitored for efficacy and safety outcomes and pharmacokinetics. The primary endpoint was ORR at 3 months, as assessed by the investigators. Secondary endpoints included DOR, PFS, OS, and adverse event frequency/severity and cell expansion kinetics. Results As of the data cutoff on 17 June 2020, 68 patients were enrolled, and 59 were treated. Among the 58 efficacy‐evaluable patients, the primary endpoint of 3 month ORR was 60.3% (95% CI, 46.6–73.0), excluding the null hypothesis rate of 20%. Any grade and severe grade CRS occurred in 47.5% and 5.1%, respectively, and any grade and severe grade neurotoxicity events occurred in 20.3% and 5.1%. Conclusions Relma‐cel met the primary endpoint analysis and demonstrated a high rate of durable responses and low rate of CAR‐T‐associated toxicities in patients with r/r LBCL in a multicenter trial supporting regulatory submission in China. The RELIANCE Trial provided the first demonstration of licensure‐quality CAR‐T manufacturing and clinical trial data generation in r/r patients originating in China. The results with relma‐cel demonstrate similar preliminary response rates and PK profiles while providing the potential for an improved toxicity profile in heavily‐pre‐treated patients with r/r DLBCL having poor risk features relative to other CD19‐specific CAR‐Ts approved in the US and EU.