CF102 for the treatment of hepatocellular carcinoma: A phase I/II, open-label, dose-escalation study.

e14731 Background: The A 3 adenosine receptor (A 3 AR) is over-expressed in hepatocellular carcinoma (HCC) cells as well as in the peripheral blood mononuclear cells (PBMCs) of patients with HCC. The orally active drug candidate CF102, an A 3 AR agonist, induces in vivo apoptosis of HCC cells via de-regulation of the Wnt signaling pathway. In this open label phase I/II trial, the safety and clinical effects of CF102 were assessed in patients with advanced unresectable HCC. Methods: The primary objectives of this trial were to examine the safety and pharmacokinetic (PK) behavior of CF102 given orally twice daily in continuous cycles of 28 days each. Evaluation of anti-tumor effects and the utilization of A 3 AR as a biological predictive marker of response to CF102 were the secondary objectives. Results: 18 patients received CF102, six at each dose level (1 mg, 5 mg and 25 mg BID). No serious drug-related adverse events or dose-limiting toxicity were observed. Most adverse events were of grade 1-2 severity. CF102 demonstrated good oral bioavailability and linear PK behavior. Median overall survival in the study population, 67% of whom were sorafenib failures, was 7.8 months (range, 3·5-27·3 months) and for Child-Pugh B patients (28%) was 8.1 months. Stable disease (SD) by RECIST was observed in four patients for at least 4 months. CF102 had no adverse effect on routine measures of liver function over a 6 months period in 12 patients. A direct correlation between A 3 AR expression levels at baseline and patients’ response to CF102 was found. Conclusions: CF102 is safe and well-tolerated and shows favorable PK characteristics and hepatoprotective effects in patients with HCC. CF102 has shown preliminary evidence of clinical activity in Child-Pugh A and B HCC patients, justifying further clinical development.