Phase I study of telatinib (BAY 57-9352): analysis of safety, pharmacokinetics, tumor efficacy, and biomarkers in patients with colorectal cancer

In this multicenter phase I dose-escalation study including a phase II like expansion part, 39 patients with refractory colorectal cancer (CRC) were enrolled into 14 days on / 7 days off in repeating cycles of 28 days (n = 11) or continuous dosing groups (n = 28) to receive ≥ 600 mg telatinib twice-daily (bid).Hypertension (28%) and diarrhoea (15%) were the most frequent study drug-related adverse events of CTC grade 3. In this population, no clear relationship between telatinib dose and individual Cmax and AUC was apparent in the 600 mg bid to 1500 mg bid dose range. No partial remission according to RECIST was reached, but 41% of the patients reached some tumour shrinkage during treatment. Tumour blood flow measured by dynamic contrast-enhanced magnetic resonance imaging and sVEGFR-2 plasma levels decreased with increasing telatinib AUC(0-12).Telatinib treatment was well tolerated. The observed single agent antitumor activity in heavily pretreated CRC patients was limited. Pharmacodynamic results are suggestive for the biological activity of telatinib justifying a further evaluation of telatinib bid in combination with standard chemotherapy regimens in CRC patients.Telatinib (BAY 57-9352) is an orally available, potent, small-molecule inhibitor of vascular endothelial growth factor (VEGF) receptors 2 and 3 (VEGFR-2/-3) and platelet-derived growth factor (PDGF) receptor β (PDGFR-β) tyrosine kinases. The data presented in this paper describe the results of colorectal cancer (CRC) patients from the dose escalation part and the phase II-like expansion part of a phase I dose escalation study in which patients received telatinib at doses of ≥ 600 mg bid (n = 39). Data from 19 of these 39 CRC patients were presented earlier [1].The study methods, treatment plan, patient evaluation, pharmacokinetic sampling, and pharmacodynamic measurements from the phase I dose escalation part of this study have been previously described [1] and the study assessments were not changed for