A Phase I trial of talazoparib in patients with advanced hematologic malignancies

The objective of this study was to establish the maximum tolerated dose (MTD), safety, pharmacokinetics, and anti-leukemic activity of talazoparib. This Phase I, two-cohort, dose-escalation trial evaluated talazoparib monotherapy in advanced hematologic malignancies (cohort 1: acute myeloid leukemia/myelodysplastic syndrome; cohort 2: chronic lymphocytic leukemia/mantle cell lymphoma). Thirty-three (cohort 1: n = 25; cohort 2: n = 8) patients received talazoparib (0.1–2.0 mg once daily). The MTD was exceeded at 2.0 mg/day in cohort 1 and at 0.9 mg/day in cohort 2. Grade ≥3 adverse events were primarily hematologic. Eighteen (54.5%) patients reported stable disease. Talazoparib is relatively well tolerated in hematologic malignancies, with a similar MTD as in solid tumors, and shows preliminary anti leukemic activity. Clinical trial registration: (ClinicalTrials.gov) The objective of this study was to define the highest dose of talazoparib that people with various types of leukemia (mainly various blood cancers) could tolerate. People were assigned into two cohorts based on their type of leukemia: cohort 1 included 25 people with acute myeloid leukemia or myelodysplastic syndrome; cohort 2 included 8 people with chronic lymphocytic leukemia or mantle cell lymphoma. Similar to what researchers observed for people with solid tumors, the highest tolerated dose was 1.35 mg per day in cohort 1, and it was estimated to be ∼0.9 mg per day in cohort 2. Side effects that occurred during the study were expected, given the types of leukemia being treated. Talazoparib also showed promising anti leukemic effects in some patients. In this Phase I talazoparib trial in hematologic malignancies (cohort 1: AML/MDS, n = 25; cohort 2: CLL/MCL, n = 8), the maximum tolerated dose was exceeded at 2.0 and 0.9 mg/day in cohorts 1 and 2, respectively. Stable disease and transfusion independence were also observed.