The Myeloid Malignancies Pipeline

Below is a list of agents currently under investigation for the treatment of myeloid malignancies, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), blastic plasmacytoid dendritic cell neoplasm (BPDCN), and MDS/MPN overlap syndromes, including chronic myelomonocytic leukemia (CMML). Information was gathered from ClinicalTrials.gov, as well as the respective drug manufacturers. For a comprehensive list of agents being evaluated for these conditions, please consult ClinicalTrials.gov.


Monoclonal Antibodies

Vadastuximab talirine: a CD33-directed antibody-drug conjugate for the treatment of treatment-naïve MDS (phase I/II) and AML (phase III)

Iomab-B: a CD45-targeting radioisotope-conjugated antibody for use as an induction and conditioning agent prior to hematopoietic cell transplantation in relapsed/refractory AML (phase III)

SL-401: an anti-IL-3 receptor antibody for the treatment of BPDCN (phase I/II)
OPN-305: an anti-TLR2 monoclonal antibody for the treatment of lower-risk MDS (phase I/II)

Talacotuzumab: an anti-CD123 monoclonal antibody for the treatment of relapsed/refractory, lower-risk MDS and AML (phase II)

Durvalumab: for the treatment of previously treated MDS (phase I) and treatment-naïve higher-risk MDs and AML in older patients (phase II)

MBG-453: an anti-TIM3 monoclonal antibody for the treatment of relapsed/refractory AML or high-risk MDS (phase I)


Kinase Inhibitors

Midostaurin: a multi-targeted kinase inhibitor for the treatment of newly diagnosed FLT3-mutant AML (phase III) and advanced systemic mastocytosis (phase II)

Quizartinib: a tyrosine kinase inhibitor for the treatment of newly diagnosed or relapsed/refractory FLT3/ITD AML (phase II)

Pacritinib: a JAK2/FLT3 inhibitor for the treatment of myelofibrosis (phase III)

Ponatinib: a multi-targeted kinase inhibitor for the treatment of FLT3/ITD AML (phase I/II) and CML (phase III dose-finding study)

Crenolanib: a tyrosine kinase inhibitor for the treatment of FLT3-mutant relapsed/refractory and newly diagnosed AML (phase II)

Alvocidib: a flavonoid alkaloid CDK9 kinase inhibitor for the treatment of newly diagnosed AML (phase II) and CML (phase I)

BLU-285: a KIT D816V oral inhibitor for the treatment of advanced systemic mastocytosis and relapsed/refractory myeloid malignancies (phase I)

NS-018: a JAK2 inhibitor for the treatment of myelofibrosis (phase I/II)

Ruxolitinib: a JAK1/JAK2 inhibitor for the treatment of CMML (phase I/II)

Entospletinib: an Syk inhibitor for the treatment of relapsed/refractory or treatment-naive AML in older patients (phase I/II)

Dactolisib: a PI3K inhibitor for the treatment of relapsed/refractory AML and CML (phase I)

Buparlisib: a PI3K inhibitor for the treatment of relapsed/refractory AML (phase I/II)


Small Molecule Inhibitors

Vismodegib: a hedgehog inhibitor for the treatment of relapsed/refractory AML (phase II) and high-risk myelofibrosis (phase I/II)

Glasdegib: a hedgehog inhibitor for the treatment of relapsed/refractory myelofibrosis (phase II) and newly diagnosed MDS, AML, and CMML (phase I)

AG-221: an IDH2 inhibitor for the treatment of newly diagnosed AML (phase I) and relapsed/refractory AML (phase III)

Venetoclax: a BCL-2 inhibitor for the treatment of relapsed/refractory, high-risk MDS (phase I), previously untreated MDS (phase II), and treatment-naïve AML (phase III)

Tipifarnib: a farnesyltransferase inhibitor for the treatment of newly diagnosed AML (phase II/III)

Imetelstat: a first-in-class telomerase inhibitor for the treatment of myelofibrosis and MDS (phase II)

Ivosidenib: an IDH1 inhibitor for the treatment of IDH2-mutant relapsed/refractory and newly diagnosed AML (phase I)

IDH305: an IDH1 inhibitor for the treatment of IDH-mutant, newly diagnosed AML (phase I)

ASTX727: an oral cytidine deaminase inhibitor for the treatment of MDS (phase I/II)

H3B-8800: an SF3b modulator for the treatment of MDS, AML, and CMML (phase I)

Tamibarotene: a synthetic retinoid for the treatment of relapsed/refractory AML and MDS (phase II)


HDAC Inhibitor

Pracinostat: an HDAC inhibitor for the treatment of newly diagnosed AML, myelofibrosis, and MDS (phase II)

Belinostat: an HDAC inhibitor for the treatment of relapsed/refractory AML and MDS (phase I)

Entinostat: an HDAC inhibitor for the treatment of previously treated MDS (phase I) and relapsed/refractory AML and CMML (phase II)


Hypomethylating Agents

Guadecitabine: a DNA methyltransferase inhibitor for the treatment of higher-risk MDS or AML (phase I/II)


CAR T-Cell Therapies

CD123 CAR T cells: CD123-directed autologous modified T cells for the treatment of relapsed/refractory CD123-positive AML or BPDCN (phase I)

CD33 CAR T cells: CD33-directed allogeneic modified T cells for the treatment of relapsed/refractory CD33-positive AML (phase I)

CD7 CAR T cells: CD7-directed allogeneic modified T cells for the treatment of relapsed/refractory AML (phase I/II)

Recombinant Fusion Proteins

Luspatercept: a recombinant fusion protein for the treatment of anemia in MDS and β-thalassemia (phase III)

Sotatercept: a recombinant fusion protein for the treatment of anemia in MDS, non-CMML, and MPNs (phase II)


Immune Checkpoint Inhibitors

Nivolumab: an anti-PD-1 monoclonal antibody for the treatment of relapsed/refractory AML (phase II) and MDS (phase II)

Pembrolizumab: an anti-PD-1 monoclonal antibody for the treatment of newly diagnosed AML (phase II), relapsed/refractory AML (phase I/II), and advanced MPNs (phase II)

Atezolizumab: an anti-PD-1 monoclonal antibody for the treatment of relapsed/refractory and treatment-naïve AML (phase I/II) and relapsed/refractory CMML (phase I/II)

CC-90002: an anti-CD47 antibody for the treatment of relapsed/refractory AML or high-risk MDS (phase I)

Hu5F9-G4: an anti-CD47 monoclonal antibody for the treatment of relapsed/refractory AML (phase I)

 

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