Triciribine (PTX-200) is an AKT inhibitor that is being tested in patients with R/R AML in combination with cytarabine. The FDA granted PTX-200 orphan drug designation in 2017. Learn more
ABBV-621 is a first-in-class, second-generation TRAIL-receptor agonist that is enrolling patients with R/R AML in the dose optimization cohort. This cohort will investigate ABBV-621 as monotherapy and in combination with venetoclax (
Fms-like tyrosine kinase 3 (FLT3) inhibitors
The phase III
ADMIRAL studyis comparing gilteritinib (ASP2215) to salvage chemotherapy in patients with R/R AML with
FLT3mutations — read the full results
here. A phase I/IIa study,
, is investigating FF-10101-01, another
FLT3inhibitor, in patients with R/R AML. Meanwhile, the
(NCT02039736) is comparing quizartinib monotherapy to salvage chemotherapy in patients with
FLT3internal tandem duplication mutated AML.
Isocitrate dehydrogenase (IDH) 1 and IDH2 inhibitors
Ivosidenib (AG-120) is an
approved by the FDAas monotherapy for patients with R/R AML with
IDH1mutations. Results in patients with newly diagnosed (ND) AML are available
and results in patients with R/R disease are available
Enasidenib is also being extensively studied in patients with
Proviral integration site of Moloney murine leukemia virus (PIM) kinase inhibitors
PIM inhibitors, such as INCB053914, are being investigated as treatments for patients with advanced malignancies like AML. One trial (
) is investigatingINCB053914 as monotherapy and in combination with standard of care (SOC) regimens: Parts 1 and 2 (monotherapy) are enrolling patients with AML that is unresponsive to current options with no SOC or curative treatment, while Parts 3 and 4 (combination cohorts) are enrolling patients with R/R AML or patients with ND AML who are aged 65 or older or who are unfit for intensive chemotherapy.
Nucleophosphomin (NPM1)-mutated AML
AMLSG 09-09 study(NCT00893399) is investigating chemotherapy with all-trans retinoic acid with or without gemtuzumab ozogamicin in patients with
EZH1 and EZH2 inhibitors
Valemetostat (DS-3201b) is an EZH1 and EZH2 inhibitor being investigated in a phase I trial (
) in patients who have failed induction therapy or relapsed following prior therapy.
Poly ADP ribose polymerase (
An example of a PARP inhibitor is talazoparib, which is being investigated in combination with decitabine in patients with both ND and R/R AML (
TET-2 mutated AML
The combination of azacitidine (a hypomethylating agent [HMA]) with ascorbic acid (vitamin C) is being investigated in patients with
TET2-mutated ND or R/R AML (
). Results from a similar study investigating the potential synergistic effects of ascorbic acid with decitabine (another HMA) are available
CBL0137 is a FACT complex-targeting curaxin under investigation as monotherapy (
). Patients with AML are being enrolled in the expansion cohort if they have > 5% blasts in the bone marrow and > 1
9/L blasts in peripheral blood.
Included within the category of new agents are immunotherapies, which utilize aspects of the body’s own immune system to recognize and attack leukemic cells.
Monoclonal antibodies (mAbs)
Hu5F9-G4 is an anti-CD47 mAb being investigated as monotherapy and in combination with azacitidine in patients with R/R AML (
).Watch David Sallman discuss whether HU5F9-G4 is a promising treatment strategy in AML below.