A novel approach for the treatment of advanced hepatocellular carcinoma (HCC).

Abstract

35 Background: No established treatments for patients with advanced HCC and moderate hepatic dysfunction (Child-Pugh B; CPB) are available. Namodenoson is an A3 adenosine-receptor agonist currently under clinical development as a treatment for advanced HCC with CPB. Methods: Wereport the results of a prospective placebo-controlled randomized (2:1) phase 2 trial investigating namodenoson (25 mg BID) as a second-line therapy in HCC with CPB and focus on a case of a long-term complete response (CR). Results: The study included 78 patients (50 namodenoson-treated, 28 placebo-treated). Namodenoson was well-tolerated and no treatment-related deaths were reported. Median overall survival (OS, the primary endpoint) was not statistically significantly different between the namodenoson and placebo arms (4.1 and 4.3 months, respectively, hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.49‒1.38; p=.46). The difference in 12-month OS was statistically significant (44% vs 18%, respectively, p=.028). Pre-planned analysis of patients with CPB7 (34 namodenoson-treated, 22 placebo-treated) showed nonsignificant improvements in OS and progression-free survival (PFS). OS: 6.9 vs 4.3 months; HR, 0.81; 95% CI: 0.45‒1.43; p=.46. PFS: 3.5 vs 1.9 months; HR, 0.89; 95% CI: 0.51‒1.55; p=.67. Of the patients with ≥1 assessment post-baseline, partial response (PR) was reported in 3 of 34 (8.8%) namodenoson-treated patients and none of the 21 placebo-treated patients. One of 3 the patients who achieved a PR (a 61-year old woman with CPB7, Barcelona Clinic Liver Cancer stage C, and Eastern Cooperative Oncology Group performance status 2) continued treatment with namodenoson under an open-label extension program (treatment is ongoing for >6 years). The patient achieved a CR (determined via CT scans) 4 years after treatment initiation. Furthermore, the patient's baseline ALT and AST levels which were elevated at baseline (68 U/L and 44 U/L, respectively) normalized after 4 weeks, and her serum α-fetoprotein level, which was 47 ng/ml at baseline, declined to normal levels after 20 weeks of treatment and reached 1.3 ng/mL at time of CR. The patient experienced no treatment-related adverse events. At present (6 years from treatment initiation), the response is ongoing as shown by liver function evaluation and imaging studies. Conclusions: Treatment with namodenoson can result in a complete and long-term response. The findings support the clinical development of namodenoson as a treatment for HCC with CPB7. Clinical trial information: NCT02128958 .