AML is a heterogeneous hematologic malignancy. For patients who are ineligible for standard treatment, relapsed from prior remission, or failed prior treatment, only few options are available for further treatment and the responses are limited. A recent study has identified dihydroorate dehydrogenase (DHODH) as a critical enzyme in the myeloid differentiation of human AML blast. At present there is no specific molecular marker to identify likely responders to DHODH inhibition. ASLAN003, a potent small molecular DHODH inhibitor, which has completed phase 1, has demonstrated the ability to induce differentiation in AML cell lines, xenograft models, and the primary AML blast obtained from patients. ASLAN003 has shown a safe and tolerable profile in prior phase I studies.
A multicenter, single arm phase IIA study to evaluate ASLAN003 as monotherapy in patients with AML who are ineligible for standard therapy. The primary objective is to determine the optimum dose of ASLAN003 based on the efficacy, safety and tolerability profile, of doses already studied in healthy volunteers. Safety will be assessed based on Adverse Events and other safety measures including vital signs, laboratory tests, electrocardiography. Efficacy will be assessed using the Overall Complete Remission Rate (OCRR, % of complete remission (CR) + complete remission with incomplete hematologic recovery (CRi)). Secondary objective is to assess the pharmacokinetics (PKs) of ASLAN003 and its metabolite and to further assess the efficacy based on relapse-free survival and clinical benefit rate (CBR, % of partial remission +CR+ CRi). Exploratory objectives is to exam the myeloid differentiation effects of ASLAN003 ex vivo and explore the possible relationships between the clinical response and AML molecular profile. The study contains 3 cohorts (ASLAN003 100 mg, 200 mg, and 300 mg once daily). Accrual has started on December 2017, with planned enrollment for 6 patients for each cohort. Safety data will be listed and summarized. Overall AML response data will be listed and summarized showing frequency and proportion of the best response, OCRR and CBR by dose levels. Concentrations and PK parameters will be listed and summarized using descriptive statistics.
Clinical trial identification
Clinical trial information: NCT03451084.
Legal entity responsible for the study
M. McHale: Chief Operating Officer and holds stocks: ASLAN Pharmaceuticals. H-J. Shih, J. Kwek: Employee: ASLAN Pharmaceuticals. N. McIntyre: Statistical consultant: Aslan Pharmaceuticals. B. Lindmark: Employee, senior management team and CMO: ASLAN Pharmaceuticals; Holds stock and stock options: ASLAN Pharmaceuticals. All other authors have declared no conflicts of interest.