Delving into the Latest Updates on Anti BCMA CART cell therapy(Shanghai YaKe Biotechnology Co Ltd) with Synapse

Overview

Basic Info

Drug Type

CAR-T

Synonyms

Anti BCMA CART cell therapy, BCMA-CART therapy

Target

4-1BB x BCMA

Mechanism

4-1BB modulators(Tumor necrosis factor receptor superfamily member 9 modulators), BCMA modulators(B-cell maturation protein modulators), Immunologic cytotoxicity

+ [1]

Therapeutic Areas

NeoplasmsImmune System DiseasesCardiovascular Diseases+ [2]

Active Indication

Multiple MyelomaRelapse multiple myelomaPlasma cell myeloma refractory

Inactive Indication-

Originator Organization

Shanghai Yake Biotechnology Co., Ltd

Active Organization

Shanghai Yake Biotechnology Co., Ltd

Zhejiang University

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy shows remarkable efficacy in patients with relapsed and/or refractory (R/R) multiple myeloma (MM). HBI0101, a novel second generation optimized anti- BCMA CAR T-cell therapy, was developed in an academic setting. We conducted a phase I dose-escalation study of HBI0101 (cohort 1: 150x106 CAR T cells, n=6; cohort 2: 450x106 CAR T cells, n=7; cohort 3: 800x106 CAR T cells, n=7) in 20 heavily pre-treated R/R MM patients. Grade 1-2 cytokine release syndrome (CRS) was reported in 18 patients (90%). Neither grade 3-4 CRS nor neurotoxicity of any grade were observed. No dose-limiting toxicities were observed in any cohort. The overall response rate (ORR), (stringent) complete response (CR/sCR), and very good partial response rates were 75%, 50%, and 25%, respectively. Response rates were dose-dependent with 85% ORR, 71% CR, and 57% minimal residual disease negativity in the high-dose cohort 3. Across all cohorts, the median overall survival (OS) was 308 days (range 25-466+), with an estimated OS of 55% as of June 27th (data cut-off). The median progression-free survival was 160 days, with 6 subjects remaining progression free at the time of data cut-off. Our findings demonstrate the manageable safety profile and efficacy of HBI0101. These encouraging data support the decentralization of CAR T production in an academic setting, ensuring sufficient CAR T supply to satisfy the increasing local demand. Clinicaltrials.gov NCT04720313.

Journal of Hematology & Oncology

Efficacy and safety of bendamustine for lymphodepletion before lisocabtagene maraleucel

Letter

Author: Gabrielli, Giulia ; Chong, Elise A ; Chong, Emeline R ; Garfall, Alfred L ; Porter, David L ; Barta, Stefan K ; Patel, Vrutti ; Carter, Jordan ; Landsburg, Daniel J ; Weber, Elizabeth ; Fardella, Eugenio ; Svoboda, Jakub ; Ruella, Marco ; Schuster, Stephen J ; Nasta, Sunita D ; White, Griffin ; Pajarillo, Raymone ; Paruzzo, Luca ; Ghilardi, Guido ; Napier, Ellen

AbstractBendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. However, bendamustine as lymphodepletion prior to lisocabtagene maraleucel (liso-cel), a 4-1BB co-stimulated, fixed CD4:CD8 ratio anti-CD19 CART product, has not been described yet. Thus, we studied a cohort of sequentially-treated patients with large B-cell lymphomas who received bendamustine lymphodepletion before liso-cel at the University of Pennsylvania between 5/2021 and 12/2023 (n = 31). Patients were evaluated for toxicities and responses. Of note, 7 patients (22.6%) would have dnot met the inclusion criteria for the registrational liso-cel clinical trials, mostly due to older age. Overall and complete response rates were 76.9% and 73.1%, respectively. At a median follow-up of 6.3 months, the 6-month progression-free and overall survival were 59.9% and 91.1%, respectively. Rates of cytokine-release syndrome (CRS) and neurotoxicity (ICANS) of any grade were 9.7% and 9.7%, respectively, with no grade ≥ 3 events. No infections were reported during the first 30 days following liso-cel infusion. Neutropenia ≥ grade 3 was observed in 29.0% of patients; thrombocytopenia ≥ grade 3 occurred in 9.7%. In conclusion, bendamustine lymphodepletion before liso-cel appears to be a strategy that can drive tumor responses while ensuring a mild toxicity profile.

Cancers

Clonal Myeloid Dysplasia Following CAR T-Cell Therapy: Chicken or the Egg?

Article

Author: Avni, Batia ; Kfir-Erenfeld, Shlomit ; Asherie, Nathalie ; Saban, Revital ; Zimran, Eran ; Horowitz, Netanel A. ; Assayag, Miri ; Gatt, Moshe E. ; Vainstein, Vladimir ; Stepensky, Polina ; Lebel, Eyal ; Rosenbluh, Chaggai ; Filanovsky, Kalman ; Auman, Shlomtzion ; Gur, Michal ; Shaulov, Adir ; Grisariu, Sigal ; Krichevsky, Svetlana ; Nachmias, Boaz

Multiple myeloma (MM) is characterized by recurrent relapses. Consequently, patients receive multiple therapy lines, including alkylating agents and immune modulators, which have been associated with secondary malignancies such as myelodysplastic syndrome (MDS). Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T cell (CART) therapy is efficacious in patients with relapsed/refractory (R/R) MM. However, the long-term complications, particularly MDS, are not well understood. Whether CART therapy causes or promotes MDS has not been thoroughly investigated. In this study, we explored the causal relationship between MDS and CART therapy. We retrospectively examined the prevalence of MDS-related morphological and mutational changes before and after administration of CART therapy in five patients. Among them, four developed MDS after CART therapy, while one had pre-existing MDS prior to CART. None of the four patients who developed post-CART MDS showed morphological MDS changes prior to CART therapy. However, all four patients exhibited molecular alterations associated with MDS in their pre-CART as well as post-CART therapy bone marrow. No new mutations were observed. Our findings provide initial evidence suggesting that anti-BCMA CART therapy in MM may promote expansion of pre-existing MDS clones rather than causing development of new clones.

100 Deals associated with Anti BCMA CART cell therapy(Shanghai YaKe Biotechnology Co Ltd)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Myeloma	Phase 2	CN	Shanghai Yake Biotechnology Co., Ltd	30 Jan 2023
Relapse multiple myeloma	Phase 1	CN	Shanghai Yake Biotechnology Co., Ltd	01 Mar 2023
Plasma cell myeloma refractory	Phase 1	CN	Shanghai Yake Biotechnology Co., Ltd	01 Jan 2021
Plasma cell myeloma refractory	Phase 1	CN	Zhejiang University	01 Jan 2021