A phase I dose finding and biomarker study of TKI258 (dovitinib lactate) in patients with advanced melanoma

9026 Background: TKI258 is an inhibitor of type III to V RTKs including VEGF-Rs, FGF-Rs (FGF-R1, 2 and 3), PDGFR-β, c- KIT and FLT3 with preclinical pharmacology profile consistent with these targets. In experimental mouse models for melanoma, TKI258 has shown efficacy as a single agent and in combination with chemotherapeutic agents. Methods: A phase I study was conducted to determine the maximum tolerated dose (MTD), the biological activity and the preliminary efficacy of TKI258 in patients with advanced melanoma. TKI258 was administered orally on a once daily continuous dose schedule in 28 days cycle. Dose escalation was governed by a two- parameter Bayesian logistic regression model. Plasma biomarkers and DCE-MRI imaging were analyzed. Results: As of November, 19 patients have been treated at the following dose levels: 200 (2), 300 (2), 400 (8) and 500 mg/d (7). Median number of cycles was 2 (0–10). Median age was 63 years (33–81), and 10 patients were male. All patients were evaluable for toxicity. 3...