aurora / FLT-3 inhib / Sareum - LARVOL DELTA

Decitabine and Sorafenib Therapy in FLT-3 ITD-Mutant Acute Myeloid Leukemia. (PubMed) - "Further investigation is warranted to confirm these responses."

Preclinical • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology • Sarcoma

Phase I/II Trial of the combination of midostaurin (PKC412) and 5-azacytidine for patients with acute myeloid leukemia and myelodysplastic syndrome. (PubMed) - "The combination of midostaurin and AZA is an effective and safe regimen in patients with AML and high-risk MDS. Patients with FLT3 mutations but not previously exposed to other FLT3 inhibitors and patients not previously transplanted derived the greatest benefit."

Journal • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Immunology • Inflammation • Myelodysplastic Syndrome • Oncology

The dual MEK/FLT3 inhibitor E6201 exerts cytotoxic activity against acute myeloid leukemia cells harboring resistance-conferring FLT3 mutations. (PubMed) - Cancer Res - "Furthermore, E6201 markedly reduced leukemia burden and improved the survival of mice in a human FLT3-mutated AML model. Collectively, our data provide a preclinical basis for the clinical evaluation of E6201 in AML patients harboring FLT3 mutations, including those who relapse following FLT3-targeted monotherapy."

Journal • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

Mechanism-Based Combinatorial Strategy for Overcoming FLT3-Inhibitor Resistance in Dual FLT3 ITD and TKD Point Mutations (ASH 2016) - "Results demonstrated massive apoptosis induction in MSC co-culture systems (apoptosis induction was 23.9% vs. 91.8% in the absence vs. presence of plerixafor). targeting FLT3/MEK and PI3K/mTOR with E6201 and voxtalisib has potential of preventing the development of FLT3-inhibitor resistance."

Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

Clonal evolution of AML on novel FMS-like tyrosine kinase-3 (FLT3) inhibitor therapy with evolving actionable targets. (PubMed) - Leuk Res Rep - "We describe novel findings alongside data on treatment directed towards actionable aberrations acquired during the process. (NCT02014558; registered at:〈https://clinicaltrials.gov/ct2/show/NCT02014558)."

Journal • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

Pre-clinical studies of gilteritinib, a next-generation FLT3 inhibitor. (PubMed) - Blood - "Our results indicate that gilteritinib overcomes many of the limitations of these other agents in that it has activity against tyrosine kinase domain (TKD) mutations and does not exhibit off-target activity against c-KIT. These features make gilteritinib potentially the most effective FLT3 TKI yet developed."

Journal • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

Updated Results from a Phase 1 Study of TAK-659, an Investigational and Reversible SYK Inhibitor, in Patients (Pts) with Advanced Solid Tumor or Lymphoma Malignancies (ASH 2016) - P1; "TAK-659, a selective, reversible, potent SYK/FLT-3 inhibitor demonstrated inhibition of SYK activity and cell proliferation in vitro and inhibited dose-dependent tumor growth in vivo in lymphoma xenograft models. Spleen tyrosine kinase (SYK), a nonreceptor kinase with a key role in B-cell receptor signaling-driven tumorigenesis, is a viable target for inhibition in B-cell malignancies. Oral TAK-659 has an acceptable PK and safety profile in pts with solid tumors or lymphoma, supporting continuous oral QD dosing. There are early signs of clinical activity in DLBCL and FL pts. Enrollment of pts with additional lymphoma subtypes is ongoing; safety and efficacy will be further investigated."

P1 data • Acute Myelogenous Leukemia • Biosimilar • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Indolent Lymphoma • Leukemia • Non-Hodgkin’s Lymphoma • Oncology

FYN expression potentiates FLT3-ITD induced STAT5 signaling in acute myeloid leukemia. (PubMed) - Oncotarget - "Taken together our data suggest that FYN cooperates with oncogenic FLT3-ITD in cellular transformation by selective activation of the STAT5 pathway. Therefore, inhibition of FYN, in combination with FLT3 inhibition, will most likely be beneficial for this group of AML patients."

Journal • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

miR-155 regulative network in FLT3 mutated acute myeloid leukemia. (PubMed) - "Our results suggest that activating mutation of FLT3 in AML can lead, through the induction of JUN, to an increased expression of miR-155, which then causes down-regulation of SPI1 and CEBPB and consequently may causes block of myeloid differentiation."

Journal • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

BEX1 acts as a tumor suppressor in acute myeloid leukemia. (PubMed) - "BEX1 localized to the cytosolic compartment of cells and significantly decreased FLT3-ITD-induced AKT phosphorylation without affecting ERK1/2 or STAT5 phosphorylation. Our data suggest that the loss of BEX1 expression in FLT3-ITD driven AML potentiates oncogenic signaling and leads to decreased overall survival of the patients."

Journal • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology