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Updated: Mar 18, 2026
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
A phase I study of BI 811283, an Aurora B kinase inhibitor, in patients with advanced solid tumors
Klaus Mross1,2, Heike Richly3, Annette Frost4,5
1Department of Medical Oncology, Tumour Biology Center, Breisacherstrasse 117, 79106, Freiburg, Germany. mross.klaus@googlemail.com.
Purpose:
This phase I study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, and antitumor activity of the Aurora B kinase inhibitor BI 811283 in patients with advanced solid tumors.
Methods:
BI 811283 was administered via 24-h infusion on Days 1 and 15 of a 4-week cycle (schedule A) or Day 1 of a 3-week cycle (schedule B) in a modified 3 + 3 dose-escalation design. Pharmacodynamic assessments included immunohistochemistry for phosphorylated histone H3 (pHH3) on skin biopsies to determine Aurora B kinase inhibition and plasma concentrations of caspase-cleaved CK-18 (apoptosis marker).
Results:
A total of 121 patients were treated. The MTDs of BI 811283 were 125 mg (schedule A) and 230 mg (schedule B). Dose-limiting toxicities were primarily hematological (febrile neutropenia and grade 4 neutropenia); the most common drug-related adverse effects included neutropenia, fatigue, leukopenia, nausea, alopecia, diarrhea, and decreased appetite. A trend toward a decrease in pHH3 was observed, with increasing BI 811283 doses, indicating target engagement; there was no consistent trend regarding caspase-cleaved CK-18 levels. No objective response was observed although 19 patients in each schedule achieved clinical benefit (stable disease).
Conclusions:
BI 811283 demonstrated a generally manageable safety profile and disease stabilization in some patients.
Trial Registration:
EudraCT No: 2007-000191-17, ClinicalTrials.gov Identifier: NCT00701324.
