-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

2108 Long Term Follow-up Results of Brl-201 Phase I Study, a Crispr-Based Non-Viral PD-1 Locus Specific Integrated Anti-CD19 CAR-T Cells in Treating Relapsed or Refractory Non-Hodgkin's Lymphoma

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Biological therapies, clinical trials, non-Hodgkin lymphoma, Lymphomas, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, Lymphoid Malignancies, gene editing, Technology and Procedures
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Biao Zheng, MD, PhD1, Yongxian Hu2,3,4,5*, Jiqin Zhang, PhD1*, Mingming Zhang2,3,4,5*, Wei Li, PhD1*, Wenjun Wu, MD2,3,4,5*, Jiazhen Cui2,3,4,5*, Guoqing Wei2,4,5,6*, Bing Du, MD, PhD1,7*, Mingyao Liu, MD, PhD1,7* and He Huang2,3,4,5*

1BRL Medicine Inc., Shanghai, China
2Institute of Hematology, Zhejiang University, Hangzhou, China
3Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
4Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
5Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
6Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
7Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China


CAR-T cell products are manufactured traditionally by using virus, which leads to the potential tumorigenesis risk and makes CAR-T cell therapy expensive and time-consuming. We developed a novel approach to generate non-viral, genome-specific integrated CAR-T cells through CRISPR/Cas9, thereby breaking through both virus usage and random integration simultaneously. Here, we update long term follow up data of trial of non-viral PD1 locus specifically integrated anti-CD19 CAR-T cells (BRL-201) in patients with relapsed/refractory (r/r) Non-Hodgkin’s lymphoma (#NCT04213469). Recently, a phase I/II of BRL-201 (#NCT05741359) is ongoing with a large-scale and multi-center design to further evaluate of BRL-201 antitumor activity in lower dose level.


This phase I investigator initiated trial evaluates BRL-201 in adult patients with r/r B-NHL. Adult patients with r/r B-NHL underwent leukapheresis and a lymphodepletion chemotherapy with cyclophosphamide (500mg/m2, D -3 to -2) and fludarabine (30mg/m2, D -4 to -2) before BRL-201 infusion. Dose escalation are based on 3+3 escalation rule, including three cohorts: 2×106/kg, 4×106/kg, 6×106/kg. Besides, 3 subjects received non-standard infusion doses at 0.56~0.8 × 106/kg. The primary endpoint was the incidence of dose-limiting toxicities (DLT). The secondary endpoint was the proportion of patients achieving an objective response at 3 months as per investigator’s assessment. In the phase I/II sponsor initiated clinical trial, we employed 3+3 rule in the escalation phase.


Between May 3, 2020 and August 10, 2021, 25 patients with r/r B-NHL were enrolled and 21 received BRL-201 with a median age of 56 years (34-70) and a median of 4 (1-9) prior lines of therapy. Among all the treated patients, 17 patients (93.8%) were diagnosed with disease stage III or IV, and 13 patients (81.3%) were assessed with high-intermediate to high risk according to IPI or aaIPI score assessment. Two patients had undergone autologous hematopoietic stem cell transplantation (HSCT) and one patient had a history of primary refractory disease. Of 17 patients with pretreatment tumor samples PD-L1 expression detection, 4 (23.5%) had > 50% PD-L1 expression, 13 (76.5%) had ≤50% PD-L1 expression.

As of May 17, 2023, the median follow- up of investigaor initiated phase I study was 29.0 months (21.5-36.2 m). All of 21 (100%) patients had an objective response to BRL-201 and 18 (85.7%) patients had a complete response (CR) as best response (Fig. 1). 7 patients achieved and maintained CR at data cut-off date, among these, 3 patients had PD-L1 expression > 50%, 1 patient was negative and 3 unknown. The median duration of response(DOR) for all 21 patients was 18.6 months (95%CI:5.1, NA ) (Fig. 2a). The median progression free survival (PFS) was 20.8 (95%CI:8.2, NA) months (Fig. 2b), while the estimated median overall survival (OS) was not reached, 12-month OS rate was 76.2% (95% CI: 60%, 96.8%) (Fig. 2c). No grade 3-4 CRS and ICANS were observed. 14 patients (66.7%) experienced grade 1-2 cytokine release syndrome (CRS) and only one patient received tocilizumab. 4 patients (19.0%) experienced grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS). No new AEs/SAEs were observed during the last follow up. In the ongoing phase I study, 1 patient with DLBCL was treated with BRL-201 and no DLT observed during 28 days after infusion at dose of 2×105/kg.


Over a median follow up of 29 months, BRL-201 was demonstrated durable response with a high median PFS of 20.8 months and 12-month OS rate of 76.2%. The median OS was not reached yet for responding patients, and the safety profile was manageable. More data will be collected to prove the value of clinical usage of BRL-201.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH