This analysis of 39 CRC patients enrolled in a phase I dose escalation study with a phase II like expansion cohort showed that telatinib administered at clinically relevant doses of ≥ 600 mg bid was well tolerated in this patient population. The recommended phase II dose for the single agent therapy with telatinib of 900 mg bid continuous dosing, as defined in the all comer dose escalation part of the study, was confirmed of being well tolerated in these heavily pretreated CRC patients. Hypertension was clinically manageable in most of the patients with a standard antihypertensive treatment. Study drug-related diarrhoea led to dose reduction or study drug discontinuation followed by a restart in 4 patients. The occurrence of gastrointestinal toxicities is known for other VEGF-inhibiting compounds [2, 3].
The variability in pharmacokinetic parameters was considerable and individual patient telatinib exposure values were generally comparable in the dose range reported herein. Detailed pharmacokinetic analysis results in 71 patients covering a wider dose range of 75 mg bid to 1500 mg bid was reported earlier .
The biomarkers assessed in this study demonstrated the biological activity of telatinib. Most of the patients, 29 out of 36, showed a decrease of iAUC60 in the DCE-MRI measurements indicating an anti-angiogenic effect in tumour tissue. The angiogenic factors VEGF and sVEGFR-2 showed effects known from other VEGF-inhibiting compounds. Changes in the DCE-MRI and decreases in sVEGFR-2 were correlated to telatinib exposure. There was no correlation between the clinical outcome and the biomarker activity, only the correlation of sVEGFR-2 changes to the tumour shrinkage showed some dependency.
The treatment with single-agent telatinib showed no objective remission in patients with CRC refractory to standard chemotherapy. This is in line with phase II study results of single-agent sunitinib treatment in CRC patients . However, one third of the CRC patients had a PFS of > 100 days, suggesting some clinical activity in this heavily pretreated patient population.
The profiles of all competitors are summarized in a review . Telatinib is currently in the clinical development for Gastric carcinoma and showed promising results in a phase II study (ref.: J Clin Oncol 28, 2010 (suppl; abstr e14575), Ko et al.).