A Study of TAS1553 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) and Other Myeloid Neoplasms

Official Title

A Phase 1 Study of Safety, Pharmacokinetics and Preliminary Activity of TAS1553 in Subjects With Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) and Other Myeloid Neoplasms

Summary:

This is a Phase 1, 2-part, open-label, multicentre, first-in-human (FIH) study to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of TAS1553 administered orally to participants ≥18 years of age with relapsed or refractory (R/R) acute myeloid leukemia (AML) or other myeloid neoplasms where approved therapies have failed or for whom known life-prolonging therapies are not available. The AML population includes de novo AML, secondary AML, and myelodysplastic syndrome (MDS)-transformed into AML. Other myeloid neoplasms include accelerated phase myeloproliferative neoplasms (MPN), and chronic or accelerated phase MPN-unclassifiable (MPN-U) and MDS-MPN. Blast crisis phase of MPNs are considered secondary AML and will be included in the AML cohort. Part 1 is a multicentre, sequential group treatment feasibility study with 1 treatment arm and no masking (dose escalation). Part 2 is a multicentre, two-stage, multiple group, dose confirmation study with 1 treatment arm and no masking (exploratory dose expansion).

Trial Description

Primary Outcome:

• Safety: Number of participants with treatment-emergent adverse events in Part 1
• Safety: Number of participants with dose-limiting toxicities in Part 1
• Response rate in Cohort 1 (AML): Number of participants with complete response (CR) + complete response with partial hematological recovery (CRh), and with CR + incomplete blood count recovery (CRi) in Part 2
• Response rate in Cohort 2 (other myeloid neoplasms): Number of participants with overall response rate (ORR) of CR + partial response (PR) in Part 2

• Pharmacokinetic parameter: Area under the curve (AUC)
• Pharmacokinetic parameter: Maximum plasma concentration (Cmax)
• Pharmacokinetic parameter: Minimum plasma concentration (Cmin)
• Pharmacokinetic parameter: Time to reach maximum plasma concentration (Tmax)
• Pharmacokinetic parameter: Half-life (t½)
• Hematological improvement: Number of participants in Cohort 2 (other myeloid neoplasms) with hematological improvement in Part 2
• Time to response (TTR): Number of days from the first dose to the first documented evidence of response
• Duration of response (DOR): Number of days from the start of response until disease progression or relapse
• Overall survival (OS): Number of days from date of first dose until death due to any cause
• Safety: Number of participants with treatment-emergent adverse events in Part 2
• Pharmacodynamic biomarker: Change from baseline in deoxyadenosine triphosphate (dATP) pool levels in peripheral blood mononuclear cells (PBMCs)
• Pharmacodynamic biomarker: Change from baseline in phosphorylated checkpoint kinase 1 (pCHK1) levels in bone marrow

View this trial on ClinicalTrials.gov