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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/25/2021.
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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/25/2021.
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Our Science

    • iberdomide (CC-220; CELMoD Agent)

    The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

    Proposed Mechanism of Action

    Iberdomide (CC-220) is an investigational cereblon E3 ligase modulator (CELMoD agent); CELMoD agents have been shown in preclinical studies to co-opt the protein cereblon (CRBN), resulting in the redirection of specific target proteins for degradation by the ubiquitin proteasome system (UPS).1,2 Iberdomide modulates CRBN such that the transcription factors Ikaros and Aiolos are degraded and led to death of cancer cells and stimulation of immune effector cells such as T cells and natural killer cells in in vitro preclinical models.3-5

    iberdomide (CC-220) by Disease State

    iberdomide (CC-220) in Multiple Myeloma

    Phase 1/2
    Relapsed/Refractory multiple myeloma

    View Trials Investigating iberdomide (CC-220) in Multiple Myeloma
    View Rationale for Clinical Development

    Rationale for Clinical Development

    Preclinical studies of iberdomide have demonstrated increased CRBN-modulating activity due to rapid and efficient substrate degradation compared with IMiD® agents.1,4 Compared with lenalidomide and pomalidomide, iberdomide demonstrated higher binding affinity for CRBN and more potent target degradation in preclinical studies.6 Iberdomide showed enhanced immune stimulatory and tumoricidal activity in multiple myeloma cell lines, including those resistant to IMiD agents, supporting further clinical development.1,4

    iberdomide (CC-220) in Lymphoma

    Phase 1
    Non-Hodgkin Lymphoma

    View Trials Investigating iberdomide (CC-220) in Lymphoma

    View Related Pathways

    Cereblon/E3 Ligase Pathway
    Cereblon E3 Ligase Modulation (CELMoD® Agents) in Targeted Protein Degradation

    References

    1. Bjorklund CC, et al. Leukemia. 2019; doi: 10.1038/s41375-019-0620-8. PMID: 31719682
    2. Collins I, et al. Biochem J. 2017;474:1127-1147. PMID: 28298557
    3. Schafer PH, et al. Ann Rheum Dis. 2018;77:1516-1523. PMID: 29945920
    4. Lonial S, et al. Blood. 2019;134(supplement_1):3119.
    5. Amantangelo M, et al. Poster presented at EHA 2019 [abstract PF559].
    6. Matyskiela ME, et al. J Med Chem. 2018;61:535-542. PMID: 28425720

    The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

     

    Proposed Mechanism of Action

    Ikaros and Aiolos (encoded by the genes IKZF1 and IKZF3, respectively) are substrates of the cullin ring ligase 4 (CRL4CRBN) E3 ubiquitin ligase complex.1 They are members of the Ikaros family of zinc-finger transcription factors and are responsible for lymphocyte differentiation and B-cell development.2,3

    Iberdomide is a cereblon (CRBN) E3 ligase modulator. CRBN is the target protein receptor on CRL4CRBN. The exact mechanism by which iberdomide exerts is therapeutic action is unknown. In preclinical studies, iberdomide was shown to redirect CRBN to induce ubiquitination and subsequent proteasomal degradation of target proteins, including Ikaros and Aiolos.2,3

    Iberdomide (CC-220) Proposed Mechanism of Action

    AutoAbs, autoantibodies CRBN, cereblon; CRL4, cullin ring ligase 4; DC, dendritic cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; IgG, immunoglobulin G; IgM, immunoglobulin M; IL, interleukin; TNF, tumor necrosis factor

    Iberdomide (CC-220) is a cereblon E3 ligase modulator that can induce degradation of transcription factors Ikaros and Aiolos2, 3

    iberdomide (CC-220) by Disease State

    iberdomide (CC-220) in Systemic Lupus Erythematosus

    Phase 1
    Systemic Lupus Erythematosus

    View Trials Investigating iberdomide (CC-220) in Systemic Lupus Erythematosus
    View Rationale for Clinical Development

    Rationale for Clinical Development

    Systemic lupus erythematosus (SLE) is a multisystem, chronic, autoimmune disorder in which different body systems are affected by inflammation.4,5 Genome-wide association studies have shown that polymorphisms in IKZF1 and IKZF3 correlated with an increased risk for developing SLE,2,3,6,7 and Ikaros and Aiolos were overexpressed in the peripheral blood.2,3 Hence, targeting Ikaros and Aiolos expression with iberdomide may have the potential to mitigate aberrant activation of B cells that result in the production of pathogenic autoantibodies associated with SLE.2,8,9

    View Related Pathways

    Cereblon/E3 Ligase Modulation

    References

    1. Gandhi AK, et al. Br J Haematol. 2014;164:811-821. PMID:24328678
    2. Schafer PH, et al. Ann Rheum Dis. 2018;77:1516-1523. PMID:29945920
    3. Nakayama Y, et al. J Immunol. 2017;199:2388-2407. PMID:28848067
    4. American College of Rheumatology. https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Lupus
    5. Lupus Foundation of America. https://www.lupus.org/resources/lupus-facts-and-statistics
    6. Cunnighame Graham DS, et al. PLoS Genet. 2011;7:e1002341. PMID:22046141
    7. Lessard CJ, et al. Am J Hum Genet. 2012;90:648-660. PMID:22464253
    8. Mok CC, Lau CS. J Clin Pathol. 2003;56:481-490. PMID:12835292
    9. Choi J, et al. Curr Opin Immunol. 2012;24:651-657. PMID:23131610