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    Home > Active Ingredient News > Blood System > GM-CSF monoclonal antibody combined with Yescarta, all CRS events are less than or equal to grade 3!

    GM-CSF monoclonal antibody combined with Yescarta, all CRS events are less than or equal to grade 3!

    • Last Update: 2021-05-09
    • Source: Internet
    • Author: User
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    Recent popular reports from Yimaike ★Faced with the high cost and low output of cell therapy, the strategy of international pharmaceutical giants to solve this challengeNew Observation of Yimai 22nd/MedClub News/--A few days ago, the clinical biopharmaceutical company Humanigen, Inc.
    reported that patients in the clinical study ZUMA-19 of the combination therapy of CAR-T therapy Yescarta (axicabtagene ciloleucel, Axi-Cel) and Lenzilumab Positive data, and based on this data plan to initiate a potential registration study.

    ZUMA-19 aims to evaluate the effectiveness and safety of Yescarta combined with Lenzilumab in the treatment of patients with relapsed/drug resistant diffuse large B-cell lymphoma (DLBCL).

    Lenzilumab is an anti-human GM-CSF monoclonal antibody.
    GM-CSF has been identified as a key factor in triggering CAR-T cell therapy-related toxicities (such as CRS and neurotoxicity).

    According to clinical correlation analysis and preclinical modeling, it is determined that Lenzilumab can inhibit GM-CSF and destroy CAR-T cell-mediated inflammation without destroying the anti-tumor ability of CAR-T cells.

    Recommended reading: Overcoming the CAR-T cytokine storm, GM-CSF monoclonal antibody obtained US patent Yimai Meng broke the news in the latest clinical data, in CAR-T cell infusion, 3 patients received a dose of 600mg Lenzilumab (Cohort 1), 3 patients received Lenzilumab at a dose of 1800 mg (Cohort 2).

    In this study, the recommended dose of Lenzilumab in the Phase 2 study was determined to be 1800 mg.

    Effectiveness: In all patients (n=6), the objective response rate (ORR) reached 83% (5/6), and the complete response rate (CR) was 66.
    67% (4/6).

    In cohort 2 (recommended dose cohort), the ORR reached 100% (3/3), and the non-toxic CR (CRS and NT events ≤ grade 2) was 66.
    67% (2/3).

    In terms of safety: In cohort 1, no patients experienced CRS ≥ grade 3, and one patient experienced grade 3 neurotoxicity (NT) for two days; in cohort 2 (recommended dose cohort), no severe CRS and NT occurred.

    Throughout the study, there were no adverse events attributable to Lenzilumab.

    At the same time, patients’ inflammatory markers are also decreasing.
    Lenzilumab dose-dependently reduces myeloid cytokines IL-6, IL-8, MCP-1 and IP-10 (CXCL-10) and systemic inflammation markers CRP, Ferritin and SAA.

    Dr.
    Dale Chappell, Chief Scientific Officer of Humanigen, said: “The encouraging results of ZUMA-19 further support our proof-of-concept.
    Lenzilumab may disrupt the link between CAR-T and toxicity and improve the durability of remission.

    We believe these positive The data is worthy of a larger study.

    "According to the press release, Humanigen will initiate a randomized, multi-center Phase 2 study to evaluate the effectiveness and safety of Lenzilumab combined with commercially available CD19 CAR-T therapy in DLBCL.
    .

    The study is expected to recruit 150 patients, and the clinical program is currently being submitted to the US FDA.

    Humanigen and Kite have terminated the clinical cooperation agreement on ZUMA-19, and the two parties will terminate the research.

    Dr.
    Cameron Durrant, CEO of Humanigen, said: "Humanigen is very pleased to develop Lenzilumab in the CAR-T therapeutic area, and thanks Kite for its sponsorship and contribution.

    "In fact, in the development of Lenzilumab, it has also been used to treat cytokine release syndrome (CRS) caused by new coronary pneumonia.
    CRS is the main cause of death in moderate/severe new coronary pneumonia.
    According

    to the data released not long ago, Lenzilumab And other therapies (including steroids and/or Gilead antiviral drug remdesivir) can improve the survival rate of hospitalized COVID-19 patients without mechanical ventilation, and the survival rate increases by 54%.

    Conclusion Cytokine Release Syndrome (CRS), In other words, the cytokine storm is a common acute side effect of CAR-T therapy.

    In fact, in 2017, when the FDA approved the marketing of Kymriah and Yescarta, it listed CRS as a black box warning for two CAR-T cell products.
    The

    same applies to the other CAR-T cells
    that have been approved for marketing.
    Although the FDA’s approval regulations have standard management methods for CRS, and according to the real-world data released by Novartis and Gilead at ASH 2019 last year, CAR- The incidence of T side effects is better than the experimental data.

    However, a series of side effects such as CRS is still a major factor restricting the development of CAR-T cells.

    Recommended reading: Consensus of seven institutions at home and abroad: CAR-T-induced CRS requires differentiated management methods, and consistent "grass-cutting" treatment may usher in new changes Yimaimeng revealed that CRS prevention and control strategies are safer CAR-T cell research directionMedical Technology This time, according to the data released by Humanigen, although the sample is small, it is undoubtedly a promising strategy! We also hope that with the efforts of many researchers, we can develop safer CAR-T cell therapy strategies, expand the accessibility of CAR-T therapy, and benefit more patients! Reference materials: 1.
    https://ir.
    humanigen.
    com/news/news-details/2021/Humanigen-Reports-Positive-Data-With-Lenzilumab-in-the-ZUMA-19-CAR-T-Phase-1b -Study-in-DLBCL-and-Plans-to-Initiate-a-Potential-Registrational-Study/default.
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