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Investigational AML Franchise edits 08 2018

Investigational AML Franchise

The investigational Acute Myeloid Leukemia (AML) Franchise of the Daiichi Sankyo Cancer Enterprise is pushing the boundaries of science aiming to define a new standard of care for patients with AML, a fast-growing form of leukemia that has the lowest 5-year survival rate of all leukemias. Advancements in the understanding of the molecular biology of AML are creating an opportunity for our researchers to discover and develop therapies that target the underlying drivers of the disease.    

Daiichi Sankyo Approach to AML

For more than 30 years, the standard of care for the treatment of AML went unchanged in part due to the complexity of the biology of AML. While new treatments have been approved recently, there is still significant unmet need and much work to be done to continue to expand the treatment options available for patients with AML.

Our investigational AML Franchise is evaluating a portfolio of therapies that leverage three distinct strategies for the treatment of AML, including quizartinib in phase 3 clinical development, milademetan (DS-3032), valemetostat (DS-3201) and PLX2853 are in phase 1 clinical development, and DS-1001 in preclinical development. Our investigational AML Franchise will evaluate combination regimens including these and other compounds for their potential to change the standard of care for patients with AML.

Relentless Focus on Transforming Science

Molecular subtyping (classifying tumors into genetically distinct categories) is creating new opportunities to better understand the science behind AML and improve on current treatment options. Our investigational AML Franchise is currently developing a portfolio of therapies that leverage three distinct strategies:

  • Growth Factor Receptor Inhibition with quizartinib, a FLT3 inhibitor in phase 3 clinical development
  • Tumor Suppressor p53 Reactivation with milademetan (DS-3032), an MDM2 inhibitor in phase 1 development
  • Targeting Epigenetic Regulation with valemetostat (DS-3201), a dual EZH1/EZH2 inhibitor in phase 1 development, PLX2853, a BRD4 inhibitor in phase 1 development, and DS-1001, a mutant IDH1 inhibitor in preclinical development

Source: Adapted from: Dohner-H et al., NEJM 2015; 373:1136-1152, Thol-F et al., Blood 2015; 126:319-327, Khan et al., Clin Can Res, 2012; Ramos-N, et al., J. Clin. Med. 2015; 4:665-695, Isidori-A et al., Can Res Frontiers 2016; 2:226-251

Pursuing multiple pathways and studying these investigational compounds in combinations with other therapies may enable us to deliver more effective treatment options and expedite development to reach patients sooner.

These are investigational agents and have not been approved by the FDA or any other regulatory agency worldwide as a treatment for any indication. Safety and efficacy have not been established.PP-US-ON-0700
05/19

Acute Myeloid Leukemia (AML) Franchise

Quizartinib:

FLT3 Inhibitor

Quizartinib, the lead agent in the investigational AML Franchise of the Daiichi Sankyo Cancer Enterprise, is an oral selective type II FLT3 inhibitor currently under regulatory review with the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the Japan Ministry of Health, Labour and Welfare (MHLW) for the treatment of adult patients with relapsed/refractory AML, which is FLT3-ITD positive.

Regulatory submission in the U.S., EU and Japan are based on the results of the pivotal phase 3 QuANTUM-R study of quizartinib versus chemotherapy in relapsed/refractory FLT3-ITD AML.

 A broad and comprehensive clinical development program is currently underway with quizartinib:

Pivotal Phase 3 Clinical Study

QuANTUM-First: Quizartinib in combination with induction and consolidation chemotherapy as well as a maintenance therapy for newly-diagnosed FLT3-ITD AML. For more information about QuANTUM-First, visit www.QuantumFirstStudy.com (US, EU and Asia)

Phase 1 Clinical Studies

Relapsed/Refractory and Newly-Diagnosed FLT3-ITD AML: Quizartinib in combination with milademetan (DS-3032) in relapsed/refractory FLT3-ITD AML or newly-diagnosed FLT3-ITD AML unfit for intensive chemotherapy (US and Japan)

Pediatric and Young Adult Relapsed/Refractory FLT3-ITD AML: Quizartinib in combination with chemotherapy as re-induction therapy in relapsed/refractory FLT3-ITD AML following intensive chemotherapy and single-agent maintenance therapy following option consolidation therapy or hematopoietic stem cell transplant (HSCT) (U.S. and EU)

Quizartinib has been granted Priority Review and Breakthrough Therapy designation for the treatment of adult patients with relapsed/refractory FLT3-ITD AML and Fast Track designation for the treatment of relapsed/refractory AML by the U.S. Food and Drug Administration (FDA).

Quizartinib also has been granted Orphan Drug designation by the FDA, the European Commission (EC) for the treatment of AML and by the Japan Ministry of Health, Labour and Welfare (MHLW) for the treatment of FLT3-mutated AML.

Milademetan (DS-3032):

MDM2 Inhibitor

 

Milademetan (DS-3032) is an investigational oral selective MDM2 inhibitor currently being evaluated in four phase 1 clinical trials for solid and hematological malignancies, including AML, acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML) in blast phase, lymphoma and myelodysplastic syndrome (MDS).

  • Relapsed/Refractory and Newly-Diagnosed FLT3-ITD AML: Milademetan (DS-3032) in combination with quizartinib in relapsed/refractory FLT3-ITD AML or newly-diagnosed FLT3-ITD AML unfit for intensive chemotherapy (US and Japan)
  • Relapsed/Refractory AML and High-Risk MDS: Milademetan as a single agent or in combination with 5-azacitidine in relapsed/refractory AML or high-risk MDS (US and Japan)
  • Solid Tumors and Lymphomas: Milademetan in advanced solid tumors or lymphomas that have relapsed from or are refractory to standard treatment or for which no standard treatment is available (US)
  • Solid Tumors and Lymphomas: Milademetan in advanced solid tumors or lymphomas that have relapsed from or are refractory to standard treatment or for which no standard treatment is available (Japan)
Valemetostat (DS-3201):

EZH1/2 Inhibitor

Valemetostat (DS-3201) is an investigational and potential first-in-class dual EZH1/2 inhibitor in phase 1 clinical development for hematologic cancers including AML, acute lymphocytic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL), including adult T-cell leukemia/lymphoma (ATL/L), peripheral T-cell lymphoma, and B-cell lymphomas. Valemetostat is currently being evaluated in two open-label phase 1 studies:

AML and ALL: Valemetostat in relapsed or refractory AML or ALL (US)

NHL : Valemetostat in NHL (adult T-cell leukemia/lymphoma or peripheral T-cell lymphoma)  that has relapsed or is refractory to standard treatment or for which no standard treatment is available (Japan)

Valemetostat has been granted SAKIGAKE Designation for the treatment of adult patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) by the Japan Ministry of Health, Labour and Welfare (MHLW).

PP-US-ON-0700
05/19

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