Crinobulin has shown promising vascular targeting activity with potent antitumor activity in both preclinical and early clinical studies, the company said. In preclinical in vitro and in vivo studies, crinobulin has been shown to induce tumor cell apoptosis and selectively inhibit growth of proliferating cell lines, including multi-drug resistant cell lines. Murine models of human tumor xenografts demonstrated that crinobulin inhibits growth of established tumors of a number of different cancer types, the company added.
In terms of clinical activity, the preliminary results of 33 patients treated in a Phase I dose escalating monotherapy study provided visible radiographic evidence of vascular disruptive activity. A variety of advanced tumor types, including hepatic, pancreatic, non-small cell lung, colon, prostate and gastrointestinal cancers, as well as metastatic melanoma, and parotid carcinoma, have been treated with crinobulin, according to the company.
Crinobulin, administered over a four-hour intravenous infusion for a cycle of three days, caused no thrombocytopenia, leucopenia, or neutropenia at any dose studied. In addition, it did not cause renal or hepatic dysfunction. Crinobulin has been well tolerated and administered for up to eight cycles with stable disease for six months duration, the company said.
EpiCept is currently evaluating the pharmacokinetic and pharmacodynamic effects of crinobulin with different dosage schedules from the Phase I study and expects to initiate a Phase Ib combination trial with crinobulin in combination with other chemotherapeutic agents in the second half of 2009.