On October 18, 2018 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported that it has initiated a Phase I study of HMPL-523, its novel spleen tyrosine kinase ("Syk") inhibitor, in combination with azacitidine, an approved nucleoside metabolic inhibitor, in elderly patients with acute myeloid leukemia ("AML") in China (Press release, Hutchison China MediTech, OCT 18, 2018, https://www.chi-med.com/phasei-hmpl523-azacitidine-aml-china/ [SID1234529956]).
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This is a Phase I, open-label, non-randomized, multicenter study to evaluate the safety, pharmacokinetics and preliminary efficacy of the combination in previously untreated elderly patients with AML who are not eligible for standard induction therapy. The primary outcome measures are overall response rate (ORR) and adverse events (AE). The two-stage study will have a dose escalation and dose expansion stage. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT03483948.
This study complements the ongoing Phase Ib dose expansion program of HMPL-523 in a broad range of hematological cancers in Australia (clinicaltrials.gov identifier: NCT02503033) and China (clinicaltrials.gov identifier: NCT02857998). These include chronic lymphocytic leukemia, small lymphocytic lymphoma, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, diffuse large B-cell lymphoma and Waldenstrom’s macroglobulinemia. Chi-Med targets to present dose escalation results at a major scientific conference later in 2018 or in 2019. Chi-Med’s U.S. Investigational New Drug (IND) application for HMPL-523 in hematological cancers was cleared by the Food and Drug Administration (FDA) at the end of June 2018 and hence Chi-Med is now planning for proof-of-concept development in the U.S.
About Syk
Syk is a non-receptor cytoplasmic tyrosine kinase primarily expressed in cells of hematopoietic lineage. Constitutive activation of Syk in AML has been reported and targeted inhibition of Syk demonstrated anti-leukemia activity in AML mouse models. Syk has also been shown to directly phosphorylate the FLT3 receptor, modulating its activation and possibly promoting its role in leukemogenesis.
About AML
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML occurs in children and adults of all ages, but is primarily a disease of older adults, with a median age at diagnosis of 67 years. AML is universally fatal without treatment, with a median survival of approximately two months.[i] The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 27%.[ii]
Combination chemotherapy regimens with or without hematopoietic stem cell transplantation (HSCT) are a mainstay of therapy for patients with newly diagnosed AML. Older patients with newly diagnosed AML who are ineligible for intensive chemotherapy typically have poor outcomes and few available treatment options. There is a clear need for new treatments for AML.