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
This is a Phase 1, 2-part, open-label, multicenter, 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 multicenter, sequential group treatment feasibility study with 1 treatment arm and no masking (dose escalation). Part 2 is a multicenter, two-stage, multiple group, dose confirmation study with 1 treatment arm and no masking (exploratory dose expansion).
• Capable of giving signed informed consent.
• Participant must be 18 years of age or older, at the time of signing the informed consent.
• Life expectancy of at least 12 weeks as assessed by the investigator.
• Participants with R/R 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 MDS transformed into AML. Other myeloid neoplasms include accelerated phase MPN, and chronic or accelerated phase MPN-U and MDS-MPN. Blast crisis phase of MPN, MPN-U, and MDS-MPN are considered secondary AML and will be included in the AML cohort.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have platelet count ≥10,000/μL (transfusions to achieve this level are allowed).
• Have adequate renal function as demonstrated by a 24-hour urine measured creatinine clearance ≥60 mL/min.
• Adequate hepatic function as evidenced by:
∙ aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN)
‣ alanine aminotransferase (ALT) ≤3×ULN
‣ total bilirubin ≤1.5×ULN.
• Participants must be amenable to serial bone marrow biopsies, peripheral blood sampling, and urine sampling during the study.
⁃ Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group \[CTFG\]) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.