^
    Back
    Association details:
    Biomarker:CD123 positive
    Cancer:Acute Myelogenous Leukemia
    Drug:pivekimab sunirine (IMGN632) (DNA replication inhibitor, CD123-targeted antibody-drug conjugate)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: C2 – Inclusion Criteria
    Source:
    clinicaltrials.gov
    Title:

    A Study of the Drug IMGN632 in Children With Leukemia That Has Come Back After Treatment or is Difficult to Treat

    Excerpt:
    ...- Patient must have leukemic blasts that are CD123-positive by flow cytometry as determined either by the treating institution or through reference laboratory testing....
    Trial ID:
    NCT05320380
    Evidence Level:
    Sensitive: C2 – Inclusion Criteria
    Source:
    clinicaltrials.gov
    Title:

    Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN

    Excerpt:
    ...Confirmation of CD123 positivity by flow cytometry or IHC....
    Trial ID:
    CADENZA
    More C2 evidence
    Evidence Level:
    Sensitive: C2 – Inclusion Criteria
    Source:
    clinicaltrialsregister.eu
    Title:

    A study of IMGN632 alone or in combination with Venetoclax and/or Azacitidine for Patients with CD123-Positive Acute Myeloid Leukemia

    Excerpt:
    ...Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry [IHC]). ...
    Trial ID:
    2019-002477-56
    Less C2 evidence
    Evidence Level:
    Sensitive: C3 – Early Trials
    Source:
    Blood
    Title:

    Clinical Profile of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate (ADC), in Patients with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

    Excerpt:
    In the assessable AML population (n=66), 37 (55%) had a reduction in bone marrow blasts, and 13 (20%) achieved an objective response (3 CR, 8 CRi, 2 MLFS; Figure 1) across a wide range of doses (0.045 to 0.3 mg/kg)….In this phase 1 trial, the novel CD123-targeting ADC IMGN632 demonstrated a manageable safety profile and broad therapeutic window in high risk R/R AML and BPDCN patients.
    DOI:
    10.1182/blood-2019-128648
    Evidence Level:
    Sensitive: D – Preclinical
    Source:
    ASH 2020
    Title:

    Combining IMGN632, a Novel CD123-Targeting Antibody Drug Conjugate with Azacitidine and Venetoclax Facilitates Apoptosis in Vitro and Prolongs Survival In Vivo in AML Models

    Published date:
    11/04/2020
    Excerpt:
    The endpoints included circulating leukemia burden monitored by hCD45/hCD123 flow cytometry of serial peripheral blood (PB) samples and mice survival....The triple combination showed superior anti-leukemic efficacy in all four PDX models, compared to IMGN632 or VEN+AZA alone (triple combination median overall survival of 152 days ± 99 days (range 41-313) vs. 131±74 days in IMGN632 (range 74-259) and 73 ± 22 days (range 51-110) in VEN+AZA....These data support the addition of a CD123-targeted ADC with a novel DNA-damaging payload to the standard of care, AZA+VEN in AML patients.
    Secondary therapy:
    venetoclax + azacitidine
    DOI:
    10.1182/blood-2020-136791
    Evidence Level:
    Sensitive: D – Preclinical
    Source:
    Blood
    Title:

    A CD123-targeting antibody-drug conjugate, IMGN632, designed to eradicate AML while sparing normal bone marrow cells

    Excerpt:
    Importantly, IMGN632 was effective at concentrations well below those that affected normal bone marrow cells, suggesting the potential for efficacy in AML patients with reduced likelihood of myelosuppressive side effects and favorable safety profile. These findings identify IMGN632 as a promising new therapeutic candidate for the treatment of this disease, and a first-in-human study in patients with relapsed/refractory CD123-positive AML 
    DOI:
    10.1182/bloodadvances.2018017517