News - CD123 expression

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.

3 days ago

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

12d

Dose-escalating Trial With Allo-RevCAR01-T Cells in Combination With CD123 Target Module (R-TM123) for Participants With Selected Hematologic Malignancies Positive for CD123 (clinicaltrials.gov)

P1, N=37, Recruiting, AvenCell Europe GmbH | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Dec 2025

12 days ago

Trial completion date • Trial primary completion date • Combination therapy

IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 expression

cyclophosphamide • fludarabine IV • AVC-201

24d

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.

24 days ago

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)

28d

Characterization of CD34+ Cells from Patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Using a t-Distributed Stochastic Neighbor Embedding (t-SNE) Protocol. (PubMed, Cancers (Basel))

Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

28 days ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • CD38 (CD38 Molecule) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD34 (CD34 molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

PD-L1 expression • CD123 expression

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.

1 month ago

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

COMPACT: COMPArative Study of the Consequence on innaTe Immune Response du to Bacterial or Viral Infection in Patients Admitted to Intensive Care Unit (clinicaltrials.gov)

P=N/A, N=38, Recruiting, University Hospital, Limoges | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

1 month ago

Trial completion date • Trial primary completion date

CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 expression

2ms

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

2 months ago

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)

2ms

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.

2 months ago

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

2ms

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.

2 months ago

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)

3ms

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.

3 months ago

Review • Journal

CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 expression • CD123 overexpression • IL3RA expression

Elzonris (tagraxofusp-erzs)

3ms

Peptide-scFv antigen recognition domains effectively confer CAR T cell multiantigen specificity. (PubMed, Cell Rep Med)

Protein structure prediction suggests that linker length and compactness influence the functionality of the generated bispecific CARs. Thus, we present a bispecific CAR design strategy to prevent immune escape in AML that can be extended to other peptide-scFv combinations.

3 months ago

Journal • CAR T-Cell Therapy

CD123 (Interleukin 3 Receptor Subunit Alpha) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 expression

B7-H3 CAR-T

3ms

Dose-escalating Trial With Allo-RevCAR01-T Cells in Combination With CD123 Target Module (R-TM123) for Participants With Selected Hematologic Malignancies Positive for CD123 (clinicaltrials.gov)

P1, N=37, Recruiting, AvenCell Europe GmbH | Not yet recruiting --> Recruiting

3 months ago

Enrollment open

IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 expression

cyclophosphamide • fludarabine IV • AVC-201

3ms

GO-TAG: Tagraxofusp-erzs, an IL-3 Diphtheria Fusion Protein, in Combination With Gemtuzumab Ozogamicin in Patients With Relapsed/Refractory AML (clinicaltrials.gov)

P1, N=36, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting | Phase classification: P1a/1b --> P1

3 months ago

Enrollment open • Phase classification • Combination therapy

CD33 (CD33 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 expression

Mylotarg (gemtuzumab ozogamicin) • Elzonris (tagraxofusp-erzs)

4ms

Recent Advances in the Biology and CD123-Directed Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm. (PubMed, Clin Lymphoma Myeloma Leuk)

The advent of tagraxofusp has opened a new era of precision oncology in the treatment of BPDCN. Herein, we present an overview of BPDCN biology, its diagnosis, and treatment options, illustrated by clinical cases.

4 months ago

Review • Journal

CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 expression

Elzonris (tagraxofusp-erzs)

4ms

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.

4 months ago

Journal

CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD33 expression • CD123 expression • IL3RA expression

4ms

CDC123 promotes Hepatocellular Carcinoma malignant progression by regulating CDKAL1. (PubMed, Pathol Res Pract)

Moreover, CDC123 was co-expressed with the CDK5 Regulatory Subunit-Associated Protein 1 Like 1 (CDKAL1), whose mRNA level was decreased after silencing CDC123. Therefore, we hypothesized that CDC123 promotes HCC progression by regulating CDKAL1.

4 months ago

Journal

CD123 (Interleukin 3 Receptor Subunit Alpha) • CDK5 (Cyclin Dependent Kinase 5)

CD123 expression

4ms

COMPACT: COMPArative Study of the Consequence on innaTe Immune Response du to Bacterial or Viral Infection in Patients Admitted to Intensive Care Unit (clinicaltrials.gov)

P=N/A, N=38, Recruiting, University Hospital, Limoges | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

4 months ago

Trial completion date • Trial primary completion date

CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 expression

5ms

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 | Trial completion date: Nov 2023 --> May 2026 | Trial primary completion date: Nov 2023 --> May 2026

5 months ago

Trial completion date • Trial primary completion date • Metastases

PD-L1 (Programmed death ligand 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 expression

flotetuzumab (MGD006)

5ms

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

5 months ago

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)

5ms

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.

5 months ago

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

5ms

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

5 months ago

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)

5ms

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.

5 months ago

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

5ms

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.

5 months ago

Clinical

CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 expression • IL3RA expression

Venclexta (venetoclax) • Elzonris (tagraxofusp-erzs) • hydroxyurea

5ms

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.

5 months ago

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)

5ms

Diagnostic Challenges in the Leukemia Phase of Blastic Plasmacytoid Dendritic Cell Neoplasm without Skin Involvement: A Clinical and Pathological Study (ASH 2023)

Only one cycle of decitabine + CAG was given and 5 months later, the disease progressed to the leukemia phase...The latter case had ASXL1 and TET2 mutations detected by NGS analysis, achieved complete remission after receiving venetoclax + azacitidine for one cycle, followed by intermittent venoclax +demethylation agent or low-dose chemotherapy maintenance treatment and live for more than two years now... BPDCN without skin lesions is clinically rare, and its diagnosis is challenging. Comprehensive immunophenotyping and cautious interpretation of immunohistochemistry results such as dim lysozyme expression are crucial. Venetoclax-containing regimens have shown promising therapeutic effects.

5 months ago

Clinical

TP53 (Tumor protein P53) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • CD34 (CD34 molecule) • CD36 (thrombospondin receptor) • NCAM1 (Neural cell adhesion molecule 1) • CD5 (CD5 Molecule) • CD14 (CD14 Molecule) • ITGAM (Integrin, alpha M) • MME (Membrane Metalloendopeptidase) • CD7 (CD7 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • NRP1 (Neuropilin 1) • SPN (Sialophorin) • TCL1A (TCL1 Family AKT Coactivator A) • ANPEP (Alanyl Aminopeptidase, Membrane) • CLEC4C (C-Type Lectin Domain Family 4 Member C) • MPO (Myeloperoxidase)

TP53 mutation • ASXL1 mutation • TET2 mutation • CD123 positive • NCAM1 expression • CD123 expression • CD4 expression • IDH2 mutation + TP53 mutation • IL3RA positive • NCAM1 positive

Venclexta (venetoclax) • azacitidine • decitabine

5ms

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.

5 months ago

Preclinical

CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 positive • CD123 expression • IL3RA expression • IL3RA positive

5ms

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.

5 months ago

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

5ms

Immunophenotypic portrait of leukemia-associated-phenotype markers in B acute lymphoblastic leukemia. (PubMed, Cytometry B Clin Cytom)

The complexity of the phenotypic signature of lymphoblasts at diagnosis of B ALL is illustrated by the variability in the expression of LAP antigens. Knowledge of the expression levels of these markers in normal leukocytes and during normal B differentiation is crucial for an optimal interpretation of diagnostic cytometry results and serves as a basis for the biological follow-up of B ALL.

5 months ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD9 (CD9 Molecule) • CD58 (CD58 Molecule) • CEACAM6 (CEA Cell Adhesion Molecule 6) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • CD81 (CD81 Molecule)

CD9 expression • CD123 expression • CD123 overexpression • CD5 overexpression

5ms

Plasmacytoid Dendritic Cells, the Expression of the Stimulator of Interferon Genes Protein (STING) and a Possible Role of Th17 Immune Response in Cervical Lesions Mediated by Human Papillomavirus. (PubMed, Indian J Microbiol)

Cells expressing IL17 were present in three groups, more frequent in cervicitis. Considering that the casuistic is composed of women carrying HIV, this infectious agent could influence the numerical similarities of the cells studied among three groups, even in the absence of HPV.

5 months ago

Journal

CD123 (Interleukin 3 Receptor Subunit Alpha) • STING (stimulator of interferon response cGAMP interactor 1) • FOXP3 (Forkhead Box P3) • IL17A (Interleukin 17A) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 expression • IL3RA positive

6ms

IRF8 in Conjunction With CD123 and CD20 to Distinguish Lupus Erythematosus Panniculitis From Subcutaneous Panniculitis-like T-Cell Lymphoma. (PubMed, Am J Surg Pathol)

However, a panel combining IRF8, CD123, and CD20, with at least 1 positive marker was more accurate than any individual marker by receiver operating characteristic curve analysis. Our study provides a rationale for potentially including IRF8 as part of an immunohistochemical panel composed of other currently available markers used to differentiate LEP from SPTCL.

6 months ago

Journal

CD20 (Membrane Spanning 4-Domains A1) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IRF8 (Interferon Regulatory Factor 8) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

CD123 positive • CD123 expression • IL3RA positive • IRF8 expression

6ms

P1, N=30, Not yet recruiting, Fred Hutchinson Cancer Center | Initiation date: Nov 2023 --> Feb 2024

6 months ago

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)

6ms

Notable Efficacy of Co-Treatment with FHD-286, a Dual BRG1/BRM ATP-Ase Inhibitor, and Menin or BET Inhibitor, Decitabine or Venetoclax Against AML with MLL-r or Mutant NPM1 (ASH 2023)

BRG1 (SMARCA4) and BRM (SMARCA2) are the core ATPase within the multi-protein, ATP-dependent, chromatin remodeling BAF complexes that regulate gene transcription. Finally, co-treatment with FHD-286 and OTX015 or SNDX-5613 (oral gavage) was significantly more effective than each drug alone in reducing the AML burden and overall survival of mice engrafted with a separate PDX model of AML cells with mtNPM1 and FLT3-ITD, without significant toxicity. These findings demonstrate the pre-clinical efficacy of FHD-286-based rational combinations and underscore their promise against AML with MLL1r or mtNPM1.

6 months ago

Clinical • PARP Biomarker • IO biomarker

FLT3 (Fms-related tyrosine kinase 3) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • MCL1 (Myeloid cell leukemia 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PLK1 (Polo Like Kinase 1) • CASP3 (Caspase 3) • ITGAM (Integrin, alpha M) • BRD4 (Bromodomain Containing 4) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • CD99 (CD99 Molecule) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • HEXIM1 (HEXIM P-TEFb Complex Subunit 1) • MEF2C (Myocyte Enhancer Factor 2C) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • CLEC12A (C-Type Lectin Domain Family 12 Member A) • PBX3 (PBX Homeobox 3)

FLT3 mutation • NPM1 mutation • CD123 expression

Venclexta (venetoclax) • decitabine • revumenib (SNDX-5613) • birabresib (OTX015) • FHD-286

6ms

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.

6 months ago

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

6ms

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.

6 months ago

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

6ms

Bone Marrow, Laboratory, and Clinical Features in Pediatric Patients with RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancy (FPDMM) (ASH 2023)

Germline mutation in RUNX1 should be considered in pediatric patients with thrombocytopenia and/or abnormal platelet function and a hypocellular marrow with or without dysmegakaryopoiesis. Dysmegakaryopoiesis in the setting of RUNX1-FPDMM should not be overinterpreted as pediatric MDS without other supporting criteria such as MDS-defining cytogenetic/molecular abnormalities, multilineage dysplasia, or increased blasts. Patients with large deletions in RUNX1 may be missed on routine NGS testing hence proper germline testing in an experienced laboratory is recommended if suspicion is high.

6 months ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • RUNX1 (RUNX Family Transcription Factor 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • BCOR (BCL6 Corepressor) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD4 (CD4 Molecule) • JAK3 (Janus Kinase 3) • CD7 (CD7 Molecule) • EBF1 (EBF Transcription Factor 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • KDM6B (Lysine Demethylase 6B) • PRMT7 (Protein Arginine Methyltransferase 7) • GJB2 (Gap Junction Protein Beta 2)

KRAS mutation • RUNX1 mutation • BCOR mutation • JAK3 mutation • CD123 expression

6ms

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.

6 months ago

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 (CPI-0610) • tasquinimod (ABR-215050)

6ms

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.

6 months ago

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

6ms

Vaccination Using an Allogeneic Leukemia-Derived Dendritic Cell Vaccine, Maintains and Improves Frequencies of Circulating Antigen Presenting Dendritic Cells Correlating with Relapse Free and Overall Survival in AML Patients (ASH 2023)

Patients who remain in CR after vididencel treatment had highest baseline levels of HLA-DR+ CD45RA+ cells, which could be myeloid cells able to differentiate into dendritic cell subsets, as in general CD45RA+ is lost during maturation from precursor to matured dendritic cells. Vaccination might improve and induce maturation of dendritic cell subsets, such as cDC1, cDC2 and pDC, which enhance antigen capturing, processing and presentation to tumor-reactive T cells, ultimately leading to improved survival.

6 months ago

Clinical • IO biomarker

CD8 (cluster of differentiation 8) • CD123 (Interleukin 3 Receptor Subunit Alpha) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CD14 (CD14 Molecule) • ITGAM (Integrin, alpha M) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • CDK1 (Cyclin-dependent kinase 1) • CD1C (CD1c Molecule)

CD123 expression

vididencel (DCP-001)