^
    3ms
    Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer (clinicaltrials.gov)
    P1, N=1, Terminated, Celyad Oncology SA | Unknown status --> Terminated; Difficulties in patient recruitment and clinical strategy modification based on new clinical data generated in the NKR-2 early development.
    Trial termination
    |
    CYAD-01
    1year
    CYAD-01, an autologous NKG2D-based CAR T-cell therapy, in relapsed or refractory acute myeloid leukaemia and myelodysplastic syndromes or multiple myeloma (THINK): haematological cohorts of the dose escalation segment of a phase 1 trial. (PubMed, Lancet Haematol)
    Treatment with a multiple CYAD-01 infusion schedule without preconditioning is well tolerated and shows anti-leukaemic activity, although without durability outside of patients bridged to allogeneic HSCT. These phase 1 data support the proof-of-concept of targeting NKG2D ligands by CAR T-cell therapy. Further clinical studies with NKG2D-based CAR T-cells are warranted, potentially via combinatorial antigen targeted approaches, to improve anti-tumour activity.
    P1 data • Clinical Trial,Phase I • Journal • CAR T-Cell Therapy
    |
    NKG2D (killer cell lectin like receptor K1)
    |
    CYAD-01
    over2years
    Co-Expression of an shRNA Targeting MICA/Micb Improves the Clinical Activity of a NKG2D-Based CAR T in Patients with Relapsed / Refractory AML/MDS (ASH 2021)
    In clinical trials, CYAD-01 showed a good tolerability profile but with a disappointing level of clinical activity when combined with cyclophosphamide / fludarabine preconditioning (DEPLETHINK trial, NCT03466320)...The knockdown of MICA/MICB appears to have a positive contribution to the initial clinical activity of CYAD-02 as compared to that achieved with the first generation CYAD-01 CAR T, together with good safety and tolerability...One approach to further drive the potency of NKG2D-based CAR T cells would likely be armoring the CAR T through using the T cell as a vehicle to secrete cytokines alongside the CAR. Overall, shRNA knockdown technology provides a means to modify CAR T function and here shows that single shRNA can target two independent genes to enhance the phenotype of the CAR Ts.
    Clinical
    |
    NKG2D (killer cell lectin like receptor K1)
    |
    cyclophosphamide • fludarabine IV • CYAD-01 • CYAD-02
    3years
    DEPLETHINK - LymphoDEPLEtion and THerapeutic Immunotherapy With NKR-2 (clinicaltrials.gov)
    P1/2, N=21, Completed, Celyad Oncology SA | Active, not recruiting --> Completed | Trial completion date: Aug 2021 --> Feb 2021 | Trial primary completion date: Aug 2021 --> Feb 2021
    Clinical • Trial completion • Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • NKG2D (killer cell lectin like receptor K1)
    |
    TP53 mutation
    |
    fludarabine IV • CYAD-01
    over3years
    [VIRTUAL] First Results from the Dose Escalation Segment of the Phase I Clinical Study Evaluating Cyad-02, an Optimized Non Gene-Edited Engineered NKG2D CAR T-Cell Product, in Relapsed or Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients (ASH 2020)
    Results As compared to CYAD-01, CYAD-02 cell expansion in vitro was 3-fold increased...The study evaluates three dose-levels of CYAD-02 (1x108, 3x108 and 1x109 cells/infusion), administered as a single infusion after non-myeloablative preconditioning chemotherapy (cyclophosphamide 300 mg/m²/day and fludarabine 30 mg/m²/day, daily for 3 days, CyFlu) according to a classical Fibonacci 3+3 design...This next generation NKG2D CAR T-cell product is currently investigated in the CYCLE-1 Phase I study in r/r AML/MDS patient population, a difficult to target disease due in part to the absence of truly AML-specific surface antigens, its rapid clinical progression and the absence of disease control by the CyFlu preconditioning. Both the anti-MICA and MICB shRNA hairpin and the OptimAb manufacturing process for CYAD-02 aim to improve CAR T-cell persistence and clinical responses.
    Clinical • P1 data • CAR T-Cell Therapy
    |
    NKG2D (killer cell lectin like receptor K1)
    |
    fludarabine IV • CYAD-01 • CYAD-02
    over3years
    [VIRTUAL] Results from the Phase I Clinical Studies Evaluating Cyad-01, a First-Generation NKG2D CAR T-Cell Product in Relapsed or Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients (ASH 2020)
    To enhance CAR T-cell persistence, we evaluated a weekly dose schedule without preconditioning (THINK study) or the addition of cyclophosphamide and fludarabine (CyFlu) as a preconditioning regimen prior to CAR T-cell infusion (phase I DEPLETHINK study, NCT03466320)...CYAD-01 manufactured using an optimized process, OptimAb, aims to improve CAR T-cell persistence and clinical responses. The data analysis of the same CAR-T product with different manufacturing processes, with or without preconditioning chemotherapy, will provide the medical community with clinical and scientific insights to guide the future of this therapeutic modality.
    Clinical • P1 data • CAR T-Cell Therapy
    |
    IFNG (Interferon, gamma) • NKG2D (killer cell lectin like receptor K1)
    |
    fludarabine IV • CYAD-01
    over3years
    DEPLETHINK - LymphoDEPLEtion and THerapeutic Immunotherapy With NKR-2 (clinicaltrials.gov)
    P1/2, N=21, Active, not recruiting, Celyad Oncology SA | Recruiting --> Active, not recruiting | N=52 --> 21
    Clinical • Enrollment closed • Enrollment change
    |
    TP53 (Tumor protein P53) • NKG2D (killer cell lectin like receptor K1)
    |
    TP53 mutation
    |
    fludarabine IV • CYAD-01