Cesnicabtagene Autoleucel(Cesnicabtagene Autoleucel) - 药物靶点：BCMA_在研适应症：难治性多发性骨髓瘤，复发性多发性骨髓瘤_专利_临床

概要

基本信息

药物类型

通用型CAR-T

别名

靶点

BCMA

作用机制

BCMA抑制剂(B细胞成熟蛋白抑制剂)

治疗领域

肿瘤免疫系统疾病心血管疾病+ [2]

在研适应症

难治性多发性骨髓瘤复发性多发性骨髓瘤

非在研适应症-

原研机构

Institut d'Investigacions Biomèdiques August Pi I Sunyer

在研机构

Instituto De SAlud Carlos Iii De Madrid

非在研机构-

最高研发阶段临床1/2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

1

项与 Cesnicabtagene Autoleucel 相关的临床试验

NCT04309981

/ Active, not recruiting临床1/2期IIT

Pilot Study of the Infusion of Differentiated Autologous T-cells From Peripheral Blood, Expanded and Transduced With a Lentivirus to Express a Chimeric Antigen Receptor With Anti-BCMA (TNFRSF17) Specificity Humanized Conjugated With the Co-stimulatory Region 4-1BB and Signal-transduction CD3z (ARI0002h) in Patients With Relapsed/Refractory Multiple Myeloma With Previous Treatment With Proteasome Inhibitor, Immunomodulatory Drug and Anti-CD38 Monoclonal Antibody

To assess the safety and efficacy of CARTBCMA ARI0002h in patients with relapsed/refractory multiple myeloma who have received treatment with proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody.

开始日期2020-05-27

申办/合作机构

Institut d'Investigacions Biomèdiques August Pi I Sunyer

[+1]

100 项与 Cesnicabtagene Autoleucel 相关的临床结果

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100 项与 Cesnicabtagene Autoleucel 相关的转化医学

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100 项与 Cesnicabtagene Autoleucel 相关的专利（医药）

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4

项与 Cesnicabtagene Autoleucel 相关的文献（医药）

2024-05-15·Clinical Cancer Research

Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma.

Article

作者: Pérez-Amill, Lorena ; Pascal, Mariona ; Rodríguez-Lobato, Luis Gerardo ; González-Navarro, Azucena ; Tovar, Natalia ; Varea, Sara ; de Cerio, Ascensión López-Díaz ; Español-Rego, Marta ; González-Calle, Verónica ; Oliver-Caldes, Aina ; Olesti, Eulalia ; Cabañas, Valentín ; Mateos, Maria Victoria ; Cid, Joan ; Fernández de Larrea, Carlos ; Battram, Anthony M. ; Moreno, David F. ; Zabaleta, Aintzane ; Sáez-Peñataro, Joaquín ; Moraleda, José M. ; Navarro-Velázquez, Sergio ; Martin-Antonio, Beatriz ; López-Parra, Miriam ; Rosiñol, Laura ; Moreno, David F ; Rodríguez-Otero, Paula ; Juan, Manel ; Sánchez-Salinas, Andrés ; Martínez-López, Joaquín ; Reguera, Juan Luis ; Prósper, Felipe ; Paiva, Bruno ; González, Marta Sonia ; Guillén, Elena ; Inogés, Susana ; López-Corral, Lucía ; Delgado, Julio ; Martínez-Cibrian, Nuria ; Urbano-Ispizua, Álvaro ; Ortiz-Maldonado, Valentín ; López-Muñoz, Nieves

AbstractPurpose:B-cell maturation antigen (BCMA)-chimeric antigen receptor T-cells (CART) improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overcome these issues. Moreover, response biomarkers and resistance mechanisms need to be identified and addressed to improve efficacy and patient selection. Here, we present clinical and ancillary results of the 60 patients treated with the academic BCMA-CART, ARI0002h, in the CARTBCMA-HCB-01 trial.Patients and Methods:We collected apheresis, final product, peripheral blood and bone marrow samples before and after infusion. We assessed BCMA, T-cell subsets, CART kinetics and antibodies, B-cell aplasia, cytokines, and measurable residual disease by next-generation flow cytometry, and correlated these to clinical outcomes.Results:At cut-off date March 17, 2023, with a median follow-up of 23.1 months (95% CI, 9.2–37.1), overall response rate in the first 3 months was 95% [95% confidence interval (CI), 89.5–100]; cytokine release syndrome (CRS) was observed in 90% of patients (5% grades ≥3) and grade 1 immune effector cell-associated neurotoxicity syndrome was reported in 2 patients (3%). Median progression-free survival was 15.8 months (95% CI, 11.5–22.4). Surface BCMA was not predictive of response or survival, but soluble BCMA correlated with worse clinical outcomes and CRS severity. Activation marker HLA-DR in the apheresis was associated with longer progression-free survival and increased exhaustion markers correlated with poorer outcomes. ARI0002h kinetics and loss of B-cell aplasia were not predictive of relapse.Conclusions:Despite deep and sustained responses achieved with ARI0002h, we identified several biomarkers that correlate with poor outcomes.

2023-08-01·The Lancet. Oncology

Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study.

Article

作者: Jiménez, Raquel ; Reguera, Juan Luis ; González-Calle, Verónica ; Oliver-Caldés, Aina ; Inogés, Susana ; López-Parra, Miriam ; Zabaleta, Aintzane ; Rodríguez-Otero, Paula ; Cabañas, Valentín ; Tovar, Natalia ; López-Corral, Lucía ; Varea, Sara ; Delgado, Julio ; López-Díaz de Cerio, Ascensión ; Olesti, Eulàlia ; Prósper, Felipe ; Pérez-Simón, José Antonio ; Martin-Antonio, Beatriz ; Fernández de Larrea, Carlos ; Urbano-Ispizua, Alvaro ; Calvo-Orteu, Maria ; Moraleda, José M ; Rodríguez-Lobato, Luis Gerardo ; Sáez-Peñataro, Joaquín ; Juan, Manel ; Paiva, Bruno ; Pascal, Mariona ; Español-Rego, Marta ; Sánchez-Salinas, Andrés ; Rosiñol, Laura ; Mateos, María-Victoria

BACKGROUNDChimeric antigen receptor (CAR) T-cell therapy is a promising option for patients with heavily treated multiple myeloma. Point-of-care manufacturing can increase the availability of these treatments worldwide. We aimed to assess the safety and activity of ARI0002h, a BCMA-targeted CAR T-cell therapy developed by academia, in patients with relapsed or refractory multiple myeloma.METHODSCARTBCMA-HCB-01 is a single-arm, multicentre study done in five academic centres in Spain. Eligible patients had relapsed or refractory multiple myeloma and were aged 18-75 years; with an Eastern Cooperative Oncology Group performance status of 0-2; two or more previous lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody; refractoriness to the last line of therapy; and measurable disease according to the International Myeloma Working Group criteria. Patients received an initial fractionated infusion of 3 × 10⁶ CAR T cells per kg bodyweight in three aliquots (0·3, 0·9, and 1·8 × 10⁶ CAR-positive cells per kg intravenously on days 0, 3, and 7) and a non-fractionated booster dose of up to 3 × 10⁶ CAR T cells per kg bodyweight, at least 100 days after the first infusion. The primary endpoints were overall response rate 100 days after first infusion and the proportion of patients developing cytokine-release syndrome or neurotoxic events in the first 30 days after receiving treatment. Here, we present an interim analysis of the ongoing trial; enrolment has ended. This study is registered with ClinicalTrials.gov, NCT04309981, and EudraCT, 2019-001472-11.FINDINGSBetween June 2, 2020, and Feb 24, 2021, 44 patients were assessed for eligibility, of whom 35 (80%) were enrolled. 30 (86%) of 35 patients received ARI0002h (median age 61 years [IQR 53-65], 12 [40%] were female, and 18 [60%] were male). At the planned interim analysis (cutoff date Oct 20, 2021), with a median follow-up of 12·1 months (IQR 9·1-13·5), overall response during the first 100 days from infusion was 100%, including 24 (80%) of 30 patients with a very good partial response or better (15 [50%] with complete response, nine [30%] with very good partial response, and six [20%] with partial response). Cytokine-release syndrome was observed in 24 (80%) of 30 patients (all grade 1-2). No cases of neurotoxic events were observed. Persistent grade 3-4 cytopenias were observed in 20 (67%) patients. Infections were reported in 20 (67%) patients. Three patients died: one because of progression, one because of a head injury, and one due to COVID-19.INTERPRETATIONARI0002h administered in a fractioned manner with a booster dose after 3 months can provide deep and sustained responses in patients with relapsed or refractory multiple myeloma, with a low toxicity, especially in terms of neurological events, and with the possibility of a point-of-care approach.FUNDINGInstituto de Salud Carlos III (co-funded by the EU), Fundación La Caixa, and Fundació Bosch i Aymerich.

British Journal of Haematology

Serum mass spectrometry for treatment monitoring in patients with multiple myeloma receiving ARI0002h CAR T‐cells

Article

作者: Español‐Rego, Marta ; Reguera, Juan Luis ; Uribe‐Herranz, Mireia ; Pascal, Mariona ; Benítez‐Ribas, Daniel ; Puig, Noemí ; Inogés, Susana ; Tréboles, Karen ; Fernández de Larrea, Carlos ; Urbano‐Ispizua, Álvaro ; López‐Diaz de Cerio, Ascensión ; Cabañas, Valentín ; Tovar, Natalia ; Aróstegui, Juan Ignacio ; Agulló, Cristina ; Moraleda, José María ; Zabaleta, Aintzane ; Zugasti, Inés ; Mora, Génesis ; Ortiz de Landazuri, Iñaki ; Paiva, Bruno ; Rodríguez Otero, Paula ; Contreras, María Teresa ; Rodríguez‐Lobato, Luis Gerardo ; González‐Calle, Verónica ; Juan, Manel ; González, Europa Azucena ; Navarro, Sergio ; Martin‐Antonio, Beatriz ; Mateos, María Victoria ; Oliver‐Caldés, Aina ; Rosiñol, Laura ; Yagüe, Jordi ; Charry, Paola

SummaryChimeric antigen receptor (CAR) T‐cell therapies have increased the patients with relapsed/refractory multiple myeloma (RRMM) in whom standard electrophoretic techniques fail to detect the M‐protein. Quantitative immunoprecipitation mass spectrometry (QIP‐MS) can accurately measure serum M‐protein with high sensitivity, and identify interferences caused by therapeutic monoclonal antibodies. Here, we investigate the outcome of QIP‐MS in 33 patients treated with the academic BCMA‐directed CAR T‐cell ARI0002h (Cesnicabtagene Autoleucel). QIP‐MS offered more detailed insights than serum immunofixation (sIFE), identifying glycosylated M‐proteins and minor additional peaks. Moreover, the potential interferences owing to daratumumab or tocilizumab treatments were successfully detected. When analysing different assay platforms during patient's monitoring after ARI0002h administration, we observed that QIP‐MS showed a high global concordance (78.8%) with sIFE, whereas it was only moderate (55.6%) with bone marrow (BM)‐based next‐generation flow cytometry (NGF). Furthermore, QIP‐MS consistently demonstrated the lowest negativity rate across the different timepoints (27.3% vs. 60.0% in months 1 and 12, respectively). Patients with QIP‐MS(+)/BM‐based NGF(−) showed a non‐significant shorter median progression free survival than those with QIP‐MS(−)/BM‐based NGF(−). In summary, we show the first experience to our knowledge demonstrating that QIP‐MS could be particularly useful as a non‐invasive technique when evaluating response after CAR T‐cell treatment in MM.

100 项与 Cesnicabtagene Autoleucel 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
难治性多发性骨髓瘤	临床2期	西班牙	Instituto De SAlud Carlos Iii De Madrid	2020-05-27
复发性多发性骨髓瘤	临床2期	西班牙	Instituto De SAlud Carlos Iii De Madrid	2020-05-27

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EHA2024	N/A	多发性骨髓瘤 sBCMA \| circulating EVs	19	PHE885	膚窪選製壓窪鹹膚衊襯(構顧鬱鏇鑰廠選鏇鬱構) = The presence of BCMA was observed and quantified in circulating EVs (these EVs were characterized by canonical EV-associated proteins). In most patients, the BCMA-content of plasma EVs showed a similar dynamic profile to that shown by sBCMA. 餘夢鑰觸鹽襯鹹構遞遞 (醖艱繭襯憲觸遞窪願鏇 ) 更多	-	2024-05-14
EHA2024	N/A	多发性骨髓瘤 sBCMA \| circulating EVs	19	ARI0002h		-	2024-05-14
NCT04309981 (CARTBCMA-HCB-01, ASH2023)	临床1/2期	复发性多发性骨髓瘤	60	ARI0002h	(襯製鹹遞築觸構廠遞鏇) = 積簾簾糧鹽鬱齋觸餘顧廠構構觸襯範淵蓋淵觸 (糧簾選鑰鹹網製願窪衊 ) 更多	-	2023-12-11
NCT04309981 (CARTBCMA-HCB-01, EHA2022) 人工标引	临床1/2期	复发性多发性骨髓瘤	35	Cyclophosphamide+fludarabine+ARI0002H	(蓋願襯鬱膚齋壓鹹膚鏇) = 積鬱築鹹選艱範糧鑰範淵餘窪廠衊遞選觸鏇鹹 (窪鑰餘簾膚繭艱觸衊鹹 ) 更多	积极	2022-05-12
NCT04309981 (CARTBCMA-HCB-01, ASH 12021 \| ASH 22021) 人工标引	临床1/2期	复发性多发性骨髓瘤	35	ARI0002h	(遞積夢鏇膚襯壓衊構憲) = 窪簾繭夢鑰淵願艱蓋遞壓鏇蓋鏇壓蓋選繭膚網 (製遞襯顧範糧鏇選鏇網 ) 更多	积极	2021-11-05