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    DRUG CLASS:

    CCR7-targeted antibody-drug conjugate

    Related drugs:
    2ms
    Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL (clinicaltrials.gov)
    P1, N=25, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business, strategic, and development considerations and not due to any safety concerns
    Trial termination
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    JBH492
    10ms
    Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL (clinicaltrials.gov)
    P1, N=25, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Mar 2024 --> Sep 2024
    Trial primary completion date
    |
    JBH492
    1year
    Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL (clinicaltrials.gov)
    P1, N=25, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Aug 2024 --> Mar 2024
    Trial primary completion date
    |
    JBH492
    1year
    Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL (clinicaltrials.gov)
    P1, N=25, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2024 --> Aug 2024 | Trial primary completion date: Mar 2024 --> Aug 2024
    Trial completion date • Trial primary completion date
    |
    JBH492
    over1year
    Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL (clinicaltrials.gov)
    P1, N=25, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=120 --> 25 | Trial completion date: Aug 2024 --> Mar 2024 | Trial primary completion date: Aug 2024 --> Mar 2024
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
    |
    JBH492
    2years
    CD69+ Bone Marrow-Resident CD8+ T Cells Represent a Functionally Impaired Tumor-Reactive Population and Can be Restored By Blocking PD-1 and Tigit in Multiple Myeloma (ASH 2022)
    Indeed, we provide an ex vivo evidence of dual blockade of immune checkpoint receptors to enhance anti-tumor T cell responses in MM. Detailed understanding of BM-resident CD8+ T cells could provide more fundamental information for improving the current T cell-based immunotherapeutic approaches against MM.
    Clinical • PD(L)-1 Biomarker • IO biomarker
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    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD69 (CD69 Molecule) • EPAS1 (Endothelial PAS domain protein 1) • KLF4 (Kruppel-like factor 4) • CCR7 (Chemokine (C-C motif) receptor 7) • GZMB (Granzyme B) • GNLY (Granulysin) • S1PR1 (Sphingosine-1-Phosphate Receptor 1)
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    CD8 expression • HAVCR2 expression
    2years
    Profiling Immune Cells in DLBCL Patients with Mass Cytometry By Time-of-Flight (CyTOF) (ASH 2022)
    (Figure 2) Conclusions By a multidimensional CyTOF staining approach, we depicted the immune cell profile of peripheral blood in DLBCL patients, analyzed the changes of the proportion of immune cell subset, and explored the changes in differentiation and function of different immune cell subsets in depth. For the first time, we found an increase in BDCA3+CXCR3+ monocyte subpopulation in DLBCL patients, and its proportion may be closely related to the prognosis of DLBCL patients.
    Clinical • PD(L)-1 Biomarker • IO biomarker
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    CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • IL2RA (Interleukin 2 receptor, alpha) • CD163 (CD163 Molecule) • CD33 (CD33 Molecule) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CCR7 (Chemokine (C-C motif) receptor 7) • CD14 (CD14 Molecule) • CD27 (CD27 Molecule) • GZMB (Granzyme B) • ITGAM (Integrin, alpha M) • FOXP3 (Forkhead Box P3) • CXCR3 (C-X-C Motif Chemokine Receptor 3) • KLRG1 (Killer Cell Lectin Like Receptor G1)
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    PD-1 expression • CTLA4 expression
    almost3years
    Novel anti-TACI single and dual-targeting CAR T cells overcome BCMA antigen loss in multiple myeloma (AACR 2022)
    We observe that the anti-TACI scFv more proximal to the CD3ζ signaling domain has a stronger effect on CAR functionality than when this scFv is more distal. Our studies provide a potential superior therapeutic option which remains efficacious in the context of BCMA antigen loss.
    CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker
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    PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD69 (CD69 Molecule) • CCR7 (Chemokine (C-C motif) receptor 7)
    3years
    Optimization of Third Generation Chimeric Antigen Receptor T Cells Targeting ROR1 for Hematological Malignancies (ASH 2021)
    Our results demonstrate that optimization of the CAR constructs enhances T-cell effector function and cytotoxicity against ROR1+ target cells. In previous studies, 3G CARs have shown longer persistence of the transduced T cells in peripheral blood, sustained and regulated cellular activation, improved solid tumor infiltration, and positive modulation of the tumor microenvironment. Our preclinical in vitro optimization demonstrates strategies to generate 3G constructs with a progressive and modulated cytotoxic profile that may confer benefits when tested in vivo in terms of enhanced persistence and lower adverse events profile.
    CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker
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    PD-1 (Programmed cell death 1) • ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1) • CEACAM5 (CEA Cell Adhesion Molecule 5) • CD28 (CD28 Molecule) • ICOS (Inducible T Cell Costimulator) • CCR7 (Chemokine (C-C motif) receptor 7)
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    PD-1 expression • ROR1 expression • CEACAM5 expression
    over3years
    BCMA-specific ADC MEDI2228 and Daratumumab induce synergistic myeloma cytotoxicity via enhanced IFN-driven innate immune responses and expression of CD38 and NKG2D ligands (IMW 2021)
    It overcame CD38 downregulation triggered by IL6 and bone marrow stromal cell culture supernatant (BMSC- sup), via activation of STAT1-IRF1 without phosphorylation of STAT3 in immunomodulatory drugs (IMiDs)- and bortezomib-resistant MM cell lines. Taken together, our data showed that MEDI2228 restored MM sensitivity to CD38 targeting by Dara without depleting NK cells and potentiated immunogenic cell death of MM cells. These results therefore provide the mechanistic rationale for clinical evaluation of combination CD38- and BCMA-directed immunotherapies to further improve patient outcome in MM.
    IO biomarker
    |
    IL6 (Interleukin 6) • CD38 (CD38 Molecule) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • STING (stimulator of interferon response cGAMP interactor 1) • CCR7 (Chemokine (C-C motif) receptor 7) • CCL2 (Chemokine (C-C motif) ligand 2) • CSF2 (Colony stimulating factor 2) • GZMB (Granzyme B) • SOCS1 (Suppressor Of Cytokine Signaling 1) • IFIT1 (Interferon Induced Protein With Tetratricopeptide Repeats 1) • RUNX3 (RUNX Family Transcription Factor 3) • STAT1 (Signal Transducer And Activator Of Transcription 1) • CCL22 (C-C Motif Chemokine Ligand 22) • CGAS (Cyclic GMP-AMP Synthase) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • NKG2D (killer cell lectin like receptor K1)
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    CD38 expression • IRF1 expression
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    bortezomib • Darzalex (daratumumab) • MEDI2228