Preliminary results of an open-label phase I pharmacokinetic/pharmacodynamic study of JNJ26481585: Early evidence of antitumor activity

e13504 Background: JNJ26481585 is a novel orally active pan-histone deacetylase inhibitor (HDACI) which showed potent antitumor efficacy in a wide range of animal tumor models. Methods: A 2-stage accelerated titration design Phase I trial was conducted to characterize safety, establish the maximum tolerated dose (MTD) and determine pharmacokinetics in patients (pts) with refractory solid tumors, of performance status <2 and with adequate hematologic, renal, hepatic and cardiac function. The drug was administered orally, once daily in 3 weekly cycles. Results: To date, 9 pts (median age 59; range 32–74) have been treated at 4 dose levels (DL): 2 (2 pts), 4 (2 pts), 8 (3 pts), and 12 (2 pts) mg. The median number of cycles administered was 2 (range 1–9). Dose-limiting toxicity was seen at 12mg (CTCAE Grade [G] 3 non-sustained ventricular tachycardia [VT] [1 pt] and G3 fatigue [1 pt]) and the 8mg cohort is being expanded. Other toxicity observed at 12mg comprised G2 palpitations with QT prolongation (1 pt), ...