Results of a first-in-human, phase I/II trial of ASP2215, a selective, potent inhibitor of FLT3/Axl in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML).

Levis, Mark J.; Perl, Alexander E.; Altman, Jessica K.; Cortés, Jorge E.; Ritchie, Ellen K.; Larson, Richard A.; Smith, Catherine C.; Wang, Eunice S.; Strickland, Stephen A.; Litzow, Mark R.; Claxton, David F.; Schiller, Gary J.; Üstün, Celalettin; Liu, Charles; Gill, Stan; Sargent, Briana; Bahceci, Erkut

doi:10.1200/jco.2015.33.15_suppl.7003

Cited by 34 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a Phase I/II trial, 82 patients with relapsed/refractory FLT3-mutated AML, the ORR (Overall response rate) was 57%, and was 63% in the 68 patients treated with 80 mg dose or higher (49). A phase III study is ongoing comparing ASP2215 to other salvage chemotherapy.…”

Section: Gilteritinib (Asp2215 Astellas)mentioning

confidence: 95%

FLT3 Inhibitors for Treating Acute Myeloid Leukemia

Hassanein

Almahayni

Ahmed

et al. 2016

Clinical Lymphoma Myeloma and Leukemia

View full text Add to dashboard Cite

Section: Gilteritinib (Asp2215 Astellas)mentioning

confidence: 95%

FLT3 Inhibitors for Treating Acute Myeloid Leukemia

Hassanein

Almahayni

Ahmed

et al. 2016

Clinical Lymphoma Myeloma and Leukemia

View full text Add to dashboard Cite

“…Emerging clinical results indicate that targeted therapeutics can have antileukemic activity as single agents and lead to complete remissions in some patients with nonacute promyelocytic leukemia AML [45][46][47][48][49][50][51][52][53][54][55][56]. However, complete remission rates are often relatively modest and may not exceed 10 or 20%.…”

Section: Therapeutic Options Once Induction Failure Is Declaredmentioning

confidence: 99%

Should acute myeloid leukemia patients with actionable targets be offered investigational treatment after failing one cycle of standard induction therapy?

Walter

2016

Current Opinion in Hematology

View full text Add to dashboard Cite

The relative value of different treatment strategies if a first standard induction therapy cycle fails to produce complete remission is unknown. However, retreatment with the same therapy often leads to complete remission and provides a benchmark against which other approaches should be compared. Addition of investigational small molecule drugs to standard reinduction therapy in patients with actionable targets could offer an attractive therapeutic strategy in this situation that might improve outcomes and facilitate clinical drug testing.

show abstract

“…Importantly, in a colony-forming assay treatment with ASP2215 was 100-fold more potent in the AML cell line compared to normal human granulocyte-macrophage precursors, suggesting a wide therapeutic window [102]. A first-in-human phase I/II trial was conducted in patients with relapsed or refractory AML and ASP2215 was well-tolerated, with favorable PK and once daily oral dosing [103,104,105]. Pharmacodynamic evaluation has thus far focused on inhibition of FLT3 phosphorylation and assessment of AXL inhibition has not been described.…”

Section: Therapeutic Targeting Of Tam Receptorsmentioning

confidence: 99%

“…Pharmacodynamic evaluation has thus far focused on inhibition of FLT3 phosphorylation and assessment of AXL inhibition has not been described. Additionally, in this trial the overall response rate for patients with FLT3 activating mutations was 57%, compared to only 11% in FLT3 wild-type patients [104]. ASP2215 trials are ongoing, both in newly diagnosed AML patients and relapsed/refractory populations; however, without regard for AXL expression, likely due to the current lack of biomarkers to predict response to AXL inhibition in leukemia [97].…”

Section: Therapeutic Targeting Of Tam Receptorsmentioning

confidence: 99%

Targeting the TAM Receptors in Leukemia

Huey

Minson

Earp

et al. 2016

Cancers

View full text Add to dashboard Cite

Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma. TAM receptors contribute to leukemic phenotypes through activation of pro-survival signaling pathways and interplay with other oncogenic proteins such as FLT3, LYN, and FGFR3. The TAM receptors also contribute to resistance to both cytotoxic chemotherapeutics and targeted agents, making them attractive therapeutic targets. A number of translational strategies for TAM inhibition are in development, including small molecule inhibitors, ligand traps, and monoclonal antibodies. Emerging areas of research include modulation of TAM receptors to enhance anti-tumor immunity, potential roles for TYRO-3 in leukemogenesis, and the function of the bone marrow microenvironment in mediating resistance to TAM inhibition.

show abstract

Results of a first-in-human, phase I/II trial of ASP2215, a selective, potent inhibitor of FLT3/Axl in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML).

Cited by 34 publications

References 0 publications

FLT3 Inhibitors for Treating Acute Myeloid Leukemia

FLT3 Inhibitors for Treating Acute Myeloid Leukemia

Should acute myeloid leukemia patients with actionable targets be offered investigational treatment after failing one cycle of standard induction therapy?

Targeting the TAM Receptors in Leukemia

Contact Info

Product

Resources

About