Study design
tumor, DLTs, neutropenia, toxicity, toxicities
DISEASE PROGRESSION, TUMOR, NEUTROPENIA
This was an open-label, multicenter, first in-human, phase I dose-escalation study of TAK-164. Patients received TAK-164 as a single intravenous infusion with a duration of up to 2 h, on day 1 of each 21-day cycle or every 3 weeks, until disease progression, unacceptable toxicity, or withdrawal from the study. Doses of 0.004 mg/kg, 0.008 mg/kg, 0.016 mg/kg, 0.032 mg/kg, 0.064 mg/kg, 0.12 mg/kg, 0.16 mg/kg, 0.19 mg/kg, 0.25 mg/kg, and 0.32 mg/kg were planned. To guide dose escalation, a method based on a Bayesian model of modified toxicity probability interval (mTPI) was used. Dose-limiting toxicities (DLTs) occurring during the first cycle of treatment (cycle 1) at a given dose level were evaluated to determine dose escalation. Safety and tolerability data beyond cycle 1 were used to determine the RP2D. DLTs were defined as: grade 4 neutropenia (ANC < 500 cells/mmThe primary objective was to evaluate the safety of TAK-164 and determine the MTD/RP2D. Secondary objectives were to characterize TAK-164 PK and immunogenicity, and to assess efficacy as measured by ORR. Exploratory objectives included assessment of the pharmacodynamic effect of TAK-164 in tumor biopsies.