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    BIOMARKER:

    IL3RA expression

    i
    Other names: IL3RA, Interleukin 3 Receptor Subunit Alpha, CD123, Interleukin 3 Receptor, Alpha (Low Affinity), Interleukin-3 Receptor Subunit Alpha, IL-3 Receptor Subunit Alpha, IL-3R Subunit Alpha, CD123 Antigen, IL-3R-Alpha, IL3R, HIL-3Ra, IL3RAY, IL-3RA, IL3RX, IL3RY
    Entrez ID:
    3563
    Related biomarkers:
    Expression
    2ms
    CP-MGD024-01: A Study of MGD024 in Patients With Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov)
    P1, N=130, Recruiting, MacroGenics | N=90 --> 130 | Trial completion date: Mar 2025 --> Oct 2025 | Trial primary completion date: Mar 2025 --> Oct 2025
    Enrollment change • Trial completion date • Trial primary completion date
    |
    IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    MGD024
    6ms
    Clinical Characteristics and Diagnosis of Ph-Positive Mixed Phenotype Acute Leukemia. (PubMed, Clin Lab)
    Mixed phenotype acute leukemia (MPAL) is a rare type of malignant hematologic disease. Its diagnosis is based on the comprehensive evaluation of bone marrow cell morphology, immunophenotype, molecular and cytogenetic features.
    Journal • IO biomarker
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD38 (CD38 Molecule) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD22 (CD22 Molecule) • CD33 (CD33 Molecule) • CD34 (CD34 molecule) • CD9 (CD9 Molecule) • MME (Membrane Metalloendopeptidase) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • ANPEP (Alanyl Aminopeptidase, Membrane) • MPO (Myeloperoxidase)
    |
    CD38 expression • CD19 expression • CD123 expression • IL3RA expression
    6ms
    Preparation of a dual-specific antibody targeting human CD123 and exploration of its anti-acute myeloid leukemia effects (PubMed, Zhonghua Xue Ye Xue Za Zhi)
    In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123(+) tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • TNFA (Tumor Necrosis Factor-Alpha) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL2RA (Interleukin 2 receptor, alpha) • CD69 (CD69 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    LAMP1 expression • CD123 expression • IL3RA expression
    7ms
    Flotetuzumab as a salvage immunotherapy in advanced CD123-positive hematological malignancies, a phase 1 pilot study. (PubMed, Leuk Lymphoma)
    Responses only occurred in Cohort B, with a partial response in one patient with Hodgkin's lymphoma and morphological complete remission in the bone marrow in one patient with blastic plasmacytoid dendritic cell neoplasm. In conclusion, flotetuzumab had a manageable safety profile in advanced CD123-positive hematological malignancies.
    P1 data • Journal • IO biomarker • Metastases
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 positive • CD123 expression • IL3RA expression • IL3RA positive
    |
    flotetuzumab (MGD006)
    7ms
    EP300-ZNF384 transactivates IL3RA to promote the progression of B-cell acute lymphoblastic leukemia. (PubMed, Cell Commun Signal)
    Doxorubicin displayed a selective killing of EP300-ZNF384-positive B-ALL cells in vitro and in vivo. Collectively, we identify IL3RA as a direct downstream target of EP300-ZNF384, suggesting CD123 is a potent biomarker for EP300-ZNF384-driven B-ALL. Targeting CD123 may be a novel therapeutic approach to EP300-ZNF384-positive patients, alternative or, more likely, complementary to standard chemotherapy regimen in clinical setting.
    Journal
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • EP300 (E1A binding protein p300) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • STAT5A (Signal Transducer And Activator Of Transcription 5A) • ZNF384 (Zinc Finger Protein 384)
    |
    CD19 positive • CD123 expression • IL3RA expression
    |
    doxorubicin hydrochloride
    8ms
    Tagraxofusp to Eradicate Measurable Residual Disease in Patients With Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=0, Withdrawn, Jonsson Comprehensive Cancer Center | N=29 --> 0 | Not yet recruiting --> Withdrawn
    Enrollment change • Trial withdrawal
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 positive • CD123 expression • IL3RA expression
    |
    azacitidine • Elzonris (tagraxofusp-erzs)
    8ms
    Hairy cell leukemia 2024: Update on diagnosis, risk-stratification, and treatment-Annual updates in hematological malignancies. (PubMed, Am J Hematol)
    The use of chemo-immunotherapy combining cladribine (CDA) and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/refractory disease is based on the use of BRAF inhibitors (BRAFi) plus R, MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22, Bruton tyrosine kinase inhibitors (BTKi), and Bcl-2 inhibitors (Bcl-2i). However, the optimal sequence of the different treatments remains to be determined.
    Journal • IO biomarker
    |
    TP53 (Tumor protein P53) • IGH (Immunoglobulin Heavy Locus) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD22 (CD22 Molecule) • IL2RA (Interleukin 2 receptor, alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • ITGAE (Integrin Subunit Alpha E) • ITGAX (Integrin Subunit Alpha X)
    |
    TP53 mutation • BRAF V600E • BRAF V600 • IGH mutation • IL2RA expression • CD123 expression • IL3RA expression
    |
    Rituxan (rituximab) • cladribine
    8ms
    Pivekimab sunirine (IMGN632), a novel CD123-targeting antibody-drug conjugate, in relapsed or refractory acute myeloid leukaemia: a phase 1/2 study. (PubMed, Lancet Oncol)
    Pivekimab sunirine showed single-agent activity across multiple doses, with a recommended phase 2 dose of 0·045 mg/kg once every 3 weeks. These findings led to a phase 1b/2 study of pivekimab sunirine plus azacitidine and venetoclax in patients with CD123-positive acute myeloid leukaemia.
    P1/2 data • Clinical Trial,Phase II • Journal
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 positive • CD123 expression • IL3RA expression • IL3RA positive
    |
    Venclexta (venetoclax) • azacitidine • pivekimab sunirine (IMGN632)
    9ms
    Treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): focus on the use of tagraxofusp and clinical considerations. (PubMed, Leuk Lymphoma)
    In addition, we present best practices and real-world insights from clinicians in academic and community settings in the US on how they use tagraxofusp to treat BPDCN. Several case studies illustrate the efficacy of tagraxofusp and discuss its safety profile, as well as the prevention, mitigation, and management of anticipated adverse events.
    Review • Journal
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • CD123 overexpression • IL3RA expression
    |
    Elzonris (tagraxofusp-erzs)
    10ms
    Dual-targeting CD33/CD123 NANOBODY® T cell engager with potent anti-AML activity and good safety profile. (PubMed, Blood Adv)
    Depletion of CD123 and CD33 expressing cells was observed, without signs of cytokine release syndrome nor clinical signs of toxicity. Taken together, the CD33/CD123 dual-targeting NANOBODY® TCE exhibits potent and safe anti-AML activity and promises a broad patient coverage.
    Journal
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD33 expression • CD123 expression • IL3RA expression
    11ms
    Combination Chemotherapy (FLAG-Ida) With Pivekimab Sunirine (PVEK [IMGN632]) for the Treatment of Newly Diagnosed Adverse Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms (clinicaltrials.gov)
    P1, N=30, Recruiting, Fred Hutchinson Cancer Center | Not yet recruiting --> Recruiting
    Enrollment open
    |
    IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • Chr t(15;17) • IL3RA expression
    |
    cytarabine • idarubicin hydrochloride • fludarabine IV • pivekimab sunirine (IMGN632) • Starasid (cytarabine ocfosfate)
    11ms
    Bispecific CD33/CD123 targeted chimeric antigen receptor T cells for the treatment of acute myeloid leukemia. (PubMed, Mol Ther Oncolytics)
    The CD33/CD123 bispecific CAR T cells were able to control acute myeloid leukemia (AML) in a xenograft AML mouse model similar to monospecific CD33 and CD123 CAR T cells while showing no on-target off-tumor effects. Based on our findings, human CD33/CD123 bispecific CAR T cells are a promising cell-based approach to prevent AML and support clinical investigation.
    Journal • CAR T-Cell Therapy
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    MB-102
    11ms
    PEPN1812: Flotetuzumab for the Treatment of Pediatric Recurrent or Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=16, Active, not recruiting, Children's Oncology Group | N=47 --> 16 | Trial completion date: Oct 2023 --> Sep 2024
    Enrollment change • Trial completion date
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    cytarabine • flotetuzumab (MGD006) • Starasid (cytarabine ocfosfate)
    12ms
    B Cell Maturation Antigen (BCMA) As a Novel and Promising Target for Immunotherapy for Acute Myeloid Leukemia (TCT-ASTCT-CIBMTR 2024)
    We explored BCMA as a novel target for immunotherapy for AML as high levels of BCMA are found on the surfaces of AML cells. We illustrated proof of concept of BCMA directed therapy via TCE therapy both in vitro and in vivo. Thus, BCMA should be considered a promising target for immunotherapy of AML including TCEs, CAR based or antibody drug conjugate approaches.
    IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • CD20 (Membrane Spanning 4-Domains A1) • TNFRSF17 (TNF Receptor Superfamily Member 17) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    12ms
    Tagraxofusp Maintenance Post-Hematopoietic Stem Cell Transplantation Provides Long-Term Survival and Manageable Safety for a Patient with Blastic Plasmacytoid Dendritic Cell Neoplasm (ASH 2023)
    Therapy prior to allo-HCT included hydroxyurea and TAG + venetoclax + mini-HyperCVAD for 5 cycles. This case report demonstrates a patient experiencing a clinically meaningful benefit with TAG maintenance therapy after allo-HCT. Both prolonged survival and manageable safety, in this case, highlight the feasibility of long-term TAG maintenance post-allo-HCT to control BPDCN.
    Clinical
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    Venclexta (venetoclax) • Elzonris (tagraxofusp-erzs) • hydroxyurea
    12ms
    Tagraxofusp Shows Promising Anti-Tumoral Efficacy in Preclinical in Vitro Models of Myelofibrosis, Both As a Single Agent and in Combination with Janus Kinase Inhibitors (ASH 2023)
    The role of the JAK/Signal transducer and activator of transcriptions (STAT) pathway in MF has led to the recent approval of three different JAK2 inhibitors (ruxolitinib, pacritinib, and fedratinib) for MF treatment. Our studies showed high sensitivity of MF cell lines to tagraxofusp as a single agent, which is expected given phase 2 results demonstrated clinical efficacy of single-agent tagraxofusp in R/R MF (Yacoub et al. ASH 2021). In addition, synergism was observed in combination with JAK inhibitors.
    Preclinical • Combination therapy
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 positive • JAK2 V617F • CD123 expression • IL3RA expression • IL3RA positive
    |
    Jakafi (ruxolitinib) • Elzonris (tagraxofusp-erzs) • Vonjo (pacritinib) • Inrebic (fedratinib)
    12ms
    Stability Assessment of Fresh or Cryopreserved Whole Blood and Bone Marrow Samples from AML and B-ALL Patients to Monitor CD123 Receptor and Immune Cells Subsets (ASH 2023)
    Based on these observations, we conclude that CD123 density, blast cells and T-cell subsets in WB and BM samples from AML patients were stable for 48 h in our experimental conditions. As a consequence, fresh WB and BM samples can be processed and analyzed by qFC within 48 h of sample collection. Furthermore, the new cryopreservation method showed sample stabilization for blasts and T cells immunophenotyping.
    Clinical • IO biomarker • Immune cell
    |
    CD38 (CD38 Molecule) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD34 (CD34 molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD38 expression • CD123 expression • IL3RA expression
    12ms
    First Disclosure of AZD9829, a TOP1i-ADC Targeting CD123: Promising Preclinical Activity in AML Models with Minimal Effect on Healthy Progenitors (ASH 2023)
    Furthermore, AZD9829 demonstrated durable blast reduction at day 28 after the first dose with leukemic blast reduction in blood (7/13 models) and in bone marrow (5/13 models). Safety studies in cynomolgus monkey support the clinical development of AZD9829, a promising therapeutic candidate for the treatment of AML across the spectrum of CD123-expression and genetic mutations.
    Preclinical
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 positive • CD123 expression • IL3RA expression • IL3RA positive
    1year
    Combination Chemotherapy (FLAG-Ida) With Pivekimab Sunirine (PVEK [IMGN632]) for the Treatment of Newly Diagnosed Adverse Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms (clinicaltrials.gov)
    P1, N=30, Not yet recruiting, Fred Hutchinson Cancer Center | Initiation date: Nov 2023 --> Feb 2024
    Trial initiation date
    |
    IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • Chr t(15;17) • IL3RA expression
    |
    cytarabine • idarubicin hydrochloride • fludarabine IV • pivekimab sunirine (IMGN632) • Starasid (cytarabine ocfosfate)
    1year
    Novel CD123xCD3 Bispecific Igm Antibody, Igm-2537, Potently Induces T-Cell Mediated Cytotoxicity of Acute Myeloid Leukemia Cells In Vivo and in Vitro with Minimal Cytokine Release (ASH 2023)
    IGM-2537 bound with high affinity and avidity to CD123. In vitro, IGM-2537 engaged both CD123 and CD3 to induce potent T-cell activation and T-cell mediated cytotoxicity of CD123+ AML cells, and autologous CD123+ basophils and plasmacytoid dendritic cells (pDCs). Though IGM-2537 demonstrated comparable maximal killing activity to a comparator IgG TCE, IGM-2537 demonstrated minimal cytokine release.
    Preclinical • IO biomarker
    |
    IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    IGM-2537
    1year
    The Impact of ZNF384 Rearranged on Antigen Editing during Treatment-Specific Selective Pressures in Adult B Cell Acute Lymphoid Leukemia (ASH 2023)
    Our findings demonstrated that ZNF384 rearrangement might induce antigen editing during treatment-related selective pressures in adult B cell acute lymphoid leukemia, especially in CAR-T therapy. More efforts are needed to reveal mechanisms behind it to help reduce antigen loss and relapse rate after CAR-T therapy.
    Clinical • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NOTCH1 (Notch 1) • CD19 (CD19 Molecule) • ETV6 (ETS Variant Transcription Factor 6) • CREBBP (CREB binding protein) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD22 (CD22 Molecule) • CD33 (CD33 Molecule) • CD34 (CD34 molecule) • EP300 (E1A binding protein p300) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • IL5 (Interleukin 5) • ZNF384 (Zinc Finger Protein 384)
    |
    FLT3-ITD mutation • CD19 expression • CD22 expression • CD33 expression • CD123 expression • IL3RA expression
    1year
    Preclinical Studies Demonstrating Efficacy of Tasquinimod in Models of Advanced Myeloproliferative Neoplasm (MPN) in Blastic Phase (ASH 2023)
    Additionally, our findings showed that co-treatment with TM (5 to 30 µM) and ruxolitinib (250 to 1000 nM), BET inhibitor OTX015 (50 to 250 nM) or pelabresib (CPI-0610) (100 to 500 nM), or BCL2/Bcl-xL inhibitor navitoclax induced synergistic lethality in advanced MPN-BP cells exhibiting delta synergy scores of >1.0 (by the ZIP method). In a separate experiment on the same PDX model, treatment with TM (30 mg/kg/day) also induced significantly greater survival advantage than treatment with ruxolitinib (30 mg/kg/day) or OTX015 (30 mg/kg/day) by oral gavage. These findings clearly demonstrate preclinical efficacy of TM in advanced MPN-BP cellular models and create the rationale to further interrogate the efficacy of TM alone and in combinations with current, front-line therapies for advanced MPN with excess blasts.
    Preclinical • PARP Biomarker • IO biomarker • Metastases
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • JAK2 (Janus kinase 2) • TERT (Telomerase Reverse Transcriptase) • CCND1 (Cyclin D1) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • IL6 (Interleukin 6) • BCL2L1 (BCL2-like 1) • TNFA (Tumor Necrosis Factor-Alpha) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • CD34 (CD34 molecule) • CDK6 (Cyclin-dependent kinase 6) • S100A8 (S100 Calcium Binding Protein A8) • S100A9 (S100 Calcium Binding Protein A9) • ITGAM (Integrin, alpha M) • TLR4 (Toll Like Receptor 4) • CALR (Calreticulin) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • CD99 (CD99 Molecule) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • NLRP3 (NLR Family Pyrin Domain Containing 3) • CLEC12A (C-Type Lectin Domain Family 12 Member A) • MPO (Myeloperoxidase)
    |
    TERT mutation • CCND1 expression • JAK2 V617F • CALR mutation • CD123 expression • IL3RA expression
    |
    Jakafi (ruxolitinib) • navitoclax (ABT 263) • birabresib (OTX015) • pelabresib (DAK539) • tasquinimod (ABR-215050)
    1year
    Updated Results from a Phase I Dose Escalation Study of the Rapidly-Switchable Universal CAR-T Therapy UniCAR-T-CD123 in Relapsed/Refractory AML (ASH 2023)
    Repeated dosing of TM in consolidation cycles resulted in robust re-expansion of UniCAR-T with deeper remissions of extended durability. The switchable mechanism provides proven rapid reversal of safety events, enabling higher dose levels.
    P1 data • IO biomarker
    |
    NPM1 (Nucleophosmin 1) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    NPM1 mutation • CD123 expression • IL3RA expression
    |
    AVC-101
    1year
    Pivekimab Sunirine (PVEK, IMGN632), a CD123-Targeting Antibody-Drug Conjugate, in Combination with Azacitidine and Venetoclax in Patients with Newly Diagnosed Acute Myeloid Leukemia (ASH 2023)
    Encouraging CCRMRD- rates were observed across cytogenetic/molecular subsets, and the majority of responding pts achieved early and deep remissions, which may translate to improved clinical outcomes. The regimen was well tolerated with no new safety signals, and the addition of PVEK to the AZA-VEN backbone did not appear to meaningfully prolong count recovery.
    Clinical • Combination therapy
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    TP53 wild-type • CD123 positive • CD123 expression • IL3RA expression • IL3RA positive
    |
    Venclexta (venetoclax) • azacitidine • pivekimab sunirine (IMGN632)
    1year
    Analysis of Tagraxofusp Activity in AML-Pdc As a Single Agent and in Combination with BCL2 Inhibitors (ASH 2023)
    Tagraxofusp was able to effectively eliminate pDCs and blasts to a lesser extent as a single agent. High expression of BCL-2 in blasts supports the consideration of tagraxofusp in combination with venetoclax as an effective combination therapy to eradicate both blasts and pDCs in AML-PDC patient samples.
    Combination therapy • IO biomarker
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • CD34 (CD34 molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    BCL2 overexpression • BCL2 expression • CD123 expression • CD123 overexpression • IL3RA expression
    |
    Venclexta (venetoclax) • Elzonris (tagraxofusp-erzs)
    1year
    Cytokine Release Syndrome Results in Reduced AML Killing By CD123 CAR T Cells (ASH 2023)
    Fludarabine and cyclophosphamide were used for lymphodepletion (LD)...Finally, we found that anti-apoptotic effects of cytokines can be prevented, and CART-123 killing of AML can be restored, via ruxolitinib blockade of JAK/STAT signaling in both in vitro and in vivo settings... We conducted a pilot study of CD123-directed CAR T cells (CART-123) in adults with relapsed or refractory AML. The primary objective was safety with a secondary objective of anti-leukemia efficacy. Twenty-two subjects were screened, and 20 were eligible for the trial.
    CAR T-Cell Therapy
    |
    FLT3 (Fms-related tyrosine kinase 3) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD4 (CD4 Molecule) • CSF2 (Colony stimulating factor 2) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
    |
    CD123 expression • CD4 expression • IL3RA expression
    |
    Jakafi (ruxolitinib) • cyclophosphamide • fludarabine IV • CART123
    1year
    A Phase II Study of Vibecotamab, a CD3-CD123 Bispecific T-Cell Engaging Antibody, for MDS or CMML after Hypomethylating Failure and in MRD-Positive AML (ASH 2023)
    Conclusion Vibecotamab was safe and active in low-blast, high-risk myeloid diseases, with a response rate of 64% in MDS/CMML after HMA failure and 25% in MRD-positive AML. The clinical activity of vibecotamab, including in pts with prior venetoclax exposure and/or HSCT, and its lack of clinically significant myelosuppression provide rationale to combine it with other agents in AML, MDS, and CMML.
    P2 data • Minimal residual disease
    |
    TP53 (Tumor protein P53) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    TP53 mutation • CD123 expression • CD123 overexpression • IL3RA expression
    |
    Venclexta (venetoclax) • vibecotamab (XmAb14045)
    1year
    Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia. (PubMed, Blood Adv)
    Response was associated with lower baseline blast count in blood and bone marrow (<25%) suggesting potential benefit. This trial was registered at www.clinicaltrials.gov as #NCT02730312.
    P1 data • Journal
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    vibecotamab (XmAb14045)
    1year
    Epitope-engineered human hematopoietic stem cells are shielded from CD123-targeted immunotherapy. (PubMed, J Exp Med)
    Transplantation of genome-edited HSPCs could enable tumor-selective targeted immunotherapy while rebuilding a fully functional hematopoietic system. We envision that this approach is broadly applicable to other targets and cells, could render hitherto undruggable targets accessible to immunotherapy, and will allow continued posttransplant therapy, for instance, to treat minimal residual disease (MRD).
    Journal • IO biomarker
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    1year
    Tagraxofusp for Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Series of Five Patients (DGHO 2023)
    Our case series is limited by a small sample size and short follow-up. However, our results provide further support for the use of tagraxofusp as a first-line therapy for BPDCN in a cohort of elderly patients with significant comorbidities.
    Clinical
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    Elzonris (tagraxofusp-erzs)
    1year
    Novel bispecific innate cell engager AFM28 efficiently directs allogenic NK cells to CD123+ leukemic blasts and stem cells in Acute Myeloid Leukemia and Myelodysplastic Neoplasms (DGHO 2023)
    AFM28 induced NK cell activation at low picomolar concentrations and mediated efficacious and significant depletion of CD123+ blasts and LSCs in primary AML and HR-MDS samples. The ability to eradicate LSCs without seriously affecting normal hematopoiesis promises durable responses and the potential for long-term remission. A phase 1 dose-escalation study of AFM28 monotherapy (NCT05817058) has been initiated and the combination with allogenic NK cells is envisioned.
    IO biomarker
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD34 (CD34 molecule) • FCGR3A (Fc Fragment Of IgG Receptor IIIa) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    AFM28
    1year
    Flotetuzumab for the Treatment of Relapsed or Refractory Advanced CD123-Positive Hematological Malignancies (clinicaltrials.gov)
    P1, N=13, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=40 --> 13
    Enrollment closed • Enrollment change • Metastases
    |
    PD-L1 (Programmed death ligand 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    flotetuzumab (MGD006)
    1year
    Study of VIP943 in Subjects With Advanced CD123+ Hematologic Malignancies (clinicaltrials.gov)
    P1, N=36, Recruiting, Vincerx Pharma, Inc. | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    VIP943
    1year
    Combination Chemotherapy (FLAG-Ida) With Pivekimab Sunirine (PVEK [IMGN632]) for the Treatment of Newly Diagnosed Adverse Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms (clinicaltrials.gov)
    P1, N=30, Not yet recruiting, Fred Hutchinson Cancer Center
    New P1 trial
    |
    IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • Chr t(15;17) • IL3RA expression
    |
    cytarabine • idarubicin hydrochloride • fludarabine IV • pivekimab sunirine (IMGN632) • Starasid (cytarabine ocfosfate)
    1year
    Study of VIP943 in Subjects With Advanced CD123+ Hematologic Malignancies (clinicaltrials.gov)
    P1, N=36, Not yet recruiting, Vincerx Pharma, Inc.
    New P1 trial • Metastases
    |
    IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    VIP943
    1year
    TAGALONG Trial: Phase II Study of Tagraxofusp and Azacitidine With or Without Venetoclax in Newly Diagnosed Secondary AML after Previous Exposure to Hypomethylating Agents (SOHO 2023)
    The null hypothesis will be rejected if 12 or more CRs are observed in 48 subjects. Continuous monitoring for toxicity will be performed.
    P2 data
    |
    CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    Venclexta (venetoclax) • azacitidine • Elzonris (tagraxofusp-erzs)
    1year
    Modeling Flotetuzumab‑Associated Cytokine Release Syndrome (CRS) in AML Using In Vitro and In Vivo Preclinical Models (SOHO 2023)
    The in vitro killing assay shows that T-cells from the spleens of immune competent C57/Bl6 hCD123eHOM mice bind to both FLZ and hCD123 on transduced murine leukemia cells. Co- culture with T-cells + target cells + FLZ showed killing at 24 hours compared to controls. T-cell activation and proliferation were noted based on cell surface markers.
    Preclinical • IO biomarker
    |
    CD8 (cluster of differentiation 8) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 expression • IL3RA expression
    |
    flotetuzumab (MGD006)
    over1year
    CADENZA: Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN (clinicaltrials.gov)
    P1/2, N=179, Active, not recruiting, ImmunoGen, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    IL3RA (Interleukin 3 Receptor Subunit Alpha)
    |
    CD123 positive • CD123 expression • IL3RA expression
    |
    pivekimab sunirine (IMGN632)