The 65th American Society of Hematology (ASH) Annual Meeting will be grandly held in San Diego, USA, from December 9 to 12, 2023. This is one of the largest and most comprehensive international conferences in the field of hematology globally, covering both malignant and non-malignant hematology. At this annual meeting, some eagerly anticipated cutting-edge research and advancements are updated every year.
On November 21, 2023, BRL Medicine announced the research on its CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection (code name: BRL-201) for the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL).Successfully Selected for the 65th American Society of Hematology Annual Meeting, and the latest data will be published in the form of a poster presentation.
Non-Hodgkin lymphoma is a malignant tumor of the hematological system that originates in lymphoid tissue, accounting for 80%-90% of all lymphomas. Although patients experience disease remission after initial treatment,There are often recurrences afterwards.. Although CAR-T products have been approved for the clinical treatment of relapsed/refractory non-Hodgkin lymphoma,The overall efficacy remains limited.。
BRL-201 is a CAR-T product targeting CD19 developed by BRL Medicine using the Quikin CART® platform, indicated for relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). Notably, this isGlobalThe First CAR-T Product Targeting CD19 with Non-Viral PD1 Site-Specific Integration, can obtain CAR-T cell products with genomic site-specific integration in a single step without using viral vectors, featuring low cost, short preparation time, simple process, high safety, and high efficacy.
The production of traditional CAR-T products mainly relies on viral vectors, which brings several prominent issues: a complex production process, high costs, long preparation cycles, and potential tumorigenic risks. In comparison, BRL Medicine's BRL-201 can effectively address the major challenges brought by the use of viral vectors, showcasing significant advantages and potential. Site-specific integration allows each CAR sequence to be precisely inserted into specific sites of the genome, avoiding the risk of tumorigenesis caused by random insertion.Maximizes the safety and efficacy of CAR-T productsWith just one step of preparation, it can simultaneously achieve the sustained expression of CAR and the regulation of endogenous genes in T cells, significantly shortening the entire CAR-T product manufacturing process. Additionally, the use of non-viral production technology offers potential cost advantages, benefiting more patients.
Code:BRL-201
Target:CD19
Manufacturer:BRL Medicine
First approved in the United States:Not yet approved
First Approval in China:Not yet approved
Clinical Data
In this Phase I trial, 25 patients with relapsed/refractory B-cell non-Hodgkin lymphoma were enrolled, of which 21 received BRL-201 treatment. The median age of the enrolled patients was 56 years; the median number of prior treatments was 4; among all treated patients, 17 (93.8%) were diagnosed with stage III or IV disease. Two patients had undergone autologous hematopoietic stem cell transplantation (HSCT), and one patient had a history of primary refractory disease. Among the 17 patients with pre-treatment tumor samples tested for PD-L1 expression, 4 (23.5%) had PD-L1 expression >50%, and 13 (76.5%) had PD-L1 expression ≤50%.
ExperimentalPrimary EndpointIs the incidence of dose-limiting toxicity (DLT);Secondary EndpointIt is the proportion of patients who achieve objective response (ORR) at 3 months based on the investigator's assessment.
As of May 17, 2023, the median follow-up time was 29.0 months, and the objective response rate (ORR) for patients treated with BRL-201 was100%, The best response is complete remission (CR), achieved85.7%Seven patients reached and maintained CR as of the data cutoff date, including 3 with PD-L1 expression >50%, 1 negative, and 3 unknown.
In addition, the median duration of response (DOR) for all patients was18.6 months. Median progression-free survival (PFS) was20.8 months, while the estimated median overall survival (OS) has not been reached, and the 12-month OS rate is76.2%。
Safety
In this trial, no grade 3-4Cytokine Release Syndrome(CRS) andImmune Effector Cell-Associated Neurotoxicity Syndrome(ICANS). CRS of grade 1-2 occurred in 14 patients (66.7%), and only one patient received tocilizumab treatment. ICANS of grade 1-2 occurred in 4 patients (19.0%). No new AEs/SAEs were observed at the last follow-up.
Summary
The trial results showed that BRL-201 demonstrated durable responses with manageable safety in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Moving forward, the researchers will gather more data to validate the clinical use value of BRL-201.
Reference Source:
https://ash.confex.com
https://www.brlmed.com
