CF102 Receives Fast Track Designation for HCC

The FDA has granted the A3AR agonist CF102 a fast track designation as a second-line treatment for patients with hepatocellular carcinoma (HCC), according to a statement from the drug's developer, Can-Fite BioPharma.

The safety and efficacy of CF102 has been assessed in an open-label phase I/II trial for patients with advanced unresectable HCC. The median overall survival (OS) was 7.8 months with CF102 in the full population. In those with CP class B tumors, the median OS was 8.1 months. At a 4-month analysis, stable disease by RECIST criteria was seen in 22% of patients. Liver function was maintained over a 6-month period.

"We are very pleased that the FDA recognizes the potential for CF102 to treat HCC patients who have tried, and not been responsive to Nexavar, the only FDA approved drug currently on the market for this indication," Pnina Fishman, PhD, chief executive officer and co-founder of Can-Fite, said in a statement. "We consider Fast Track designation to be a major catalyst for our CF102 development program and we believe it could shorten our time to market for CF102, thereby making a considerable difference for patients."

CF102 selectively binds to A3AR on the surface of cells, causing deregulation of the Wnt and NF-κB signal transduction pathways. A3AR, which plays a role in cellular proliferation, is highly expression on the surfaces of various solid tumors, specifically HCC.

The phase I/II study examined the pharmacokinetic (PK) behavior of CF102 at varying doses. Additionally, A3AR was examined as a potential predictive biomarker of response.

The study enrolled 18 patients, 28% with CP class B tumors and 67% who had received prior sorafenib. PK data demonstrated good oral bioavailable, and there were no serious adverse events or dose-limiting toxicities.

The study found a correlation between expression of A3AR and OS, warranting the initiation of further studies for a blood-based biomarker test kit. In March 18, 2015, the company announced that it had completed the development of a commercial predictive blood test for A3AR that could return results within a few hours.

“The completion of the development of our commercial A3AR biomarker test kit comes at a very important time since we plan to use the test kit in our upcoming advanced clinical studies,” said Fishman. “We believe the test kit will create efficiencies in our trials in patient enrollment and monitoring."

CF102 received an orphan drug designation as a second-line treatment for HCC in February 2012. The fast track and orphan drug designations allow Can-Fite to complete a rolling submission of data to the FDA for a new drug application.

A phase II study exploring CF102 is currently being conducted in the United States, Europe, and Israel. In this 78-patient randomized study, the agent will be compared with placebo in those with CP class B cirrhosis following progression on sorafenib. The primary endpoint of the study is OS (NCT02128958).

In addition to HCC, Can-Fite plans a phase III study for CF102 in patients with rheumatoid arthritis. Additionally, the company is planning studies for patients with advanced psoriasis. Outside of these indications, the agent has shown promise in proof-of-principle studies for patients with colon cancer, prostate cancer, and melanoma.

References

1. Stemmer SM, Benjaminov O, Medalia G, et al. CF102 for the treatment of hepatocellular carcinoma: a phase I/II, open-label, dose-escalation study.Oncologist. 2013;18(1):25-26.