AEterna Zentaris Inc. has presented a poster outlining Phase 1 results for its orally-active tubulin and topoisomerase II inhibitor compound, AEZS-112, in patients with advanced solid tumors or lymphoma, which may potentially provide a new therapeutic approach for the treatment of cancer.
The poster was presented at the American Association for Cancer Research (AACR) Annual Meeting in Denver, Colorado.
The poster (#5567) entitled, “Phase I dose-escalation, safety, and pharmacokinetic study on weekly oral AEZS-112, a small molecule anti-cancer agent in patients with advanced cancer and lymphoma”, D.W. Northfelt, reviewed results of this Phase I study designed to evaluate the safety, tolerability and pharmacokinetics of ascending doses of AEZS-112 in patients with the above-mentioned forms of cancer.
In part I, 22 patients (12 men/10 women) were studied on 7 dose levels ranging from 13 to 800 mg/week. In all, 62 treatment cycles were administered. In part II, 22 patients (12 men/10 women) were studied on 5-dose levels ranging from 120 to 600 (=200×3) mg/week. As of April 1, 2009, 62 treatment cycles were administered (mean 3.2/patient); treatment was ongoing in 8 patients. Stable disease (SD) for more than 12 weeks was observed in 16 patients; 4 more patients were ongoing at less than 12 weeks. Prolonged courses of SD ranging from 20 to 39+ weeks were observed in 9 patients with the following primary cancer types: trachea (39+), tongue (30+), thyroid (29+), prostate and melanoma (28), non-small cell lung cancer (26+), pancreas and 2x colorectal (20).
Except for one patient with a background of gastrointestinal problems (GI) who had dose-limiting GI reactions and electrolyte loss at a dose of 200x3mg/week, no clinically relevant drug-related adverse events or changes in laboratory parameters were observed. AEZS-112 was shown to be metabolically stable in human plasma. As predicted by pharmacokinetic modelling based on data from part I of the study, the split-dose scheme leads to a higher Cmax and trough values after administration of comparable doses.
AEZS-112 was well tolerated over repeated treatment courses; – So far, a maximum tolerated dose for weekly dosing has not been defined; and – Prolonged courses of stable disease in both parts of the study are an encouraging observation. About AEterna Zentaris Inc.