AEterna Zentaris Completes Phase 1 Study For Cancer

AEterna Zentaris has announced the completion of a phase 1 study of orally-active tubulin and topoisomerase II inhibitor compound, AEZS-112, in patients with advanced solid tumors or lymphoma.

The study was an open-label, dose-escalation, multi-center, intermittent treatment phase 1 study, which included patients with advanced solid tumors and lymphoma who had either failed standard therapy or for whom no standard therapy existed.

Patients received a once-a-week oral administration of AEZS-112 for three consecutive weeks, followed by a one-week period without treatment. The cycles were repeated every four weeks based on tolerability and response, basically planned for up to four cycles, but allowing for continuation in case of potential benefit for the patient.

The starting dose of AEZS-112 in this study was 13mg/week, with doubling of doses in subsequent cohorts in the absence of significant toxicity. Primary endpoints of the phase 1 trial focused on determining the safety and tolerability of AEZS-112, as well as establishing a recommended phase 2 dose and regimen. Secondary endpoints aimed at establishing the pharmacokinetics and determining the efficacy based on standard response criteria.

The study was performed in two parts and included 42 patients overall. In part I, 22 patients were studied on doses ranging from 13 to 800mg/week. In part II, the weekly dose was split into 3 doses taken 8 hours apart, and ultimately, 20 patients received doses from 120 to 600mg/week. Stable disease with time to failure ranging from 20 to 60+ weeks was achieved in 12 patients with various cancer types, including melanoma and cancers of the colon/rectum, lung, pancreas, prostate, tongue, trachea and thyroid.

In several of these patients, the duration of stabilisation exceeded the duration of disease control on previous treatment regimens. Except for a dose-limiting gastrointestinal reaction in a patient with pre-existing GI problems, no clinically relevant drug-related adverse events or changes in laboratory safety parameters were observed.

Paul Blake, senior vice president and chief medical officer of AEterna Zentaris, said: “We are pleased with these phase 1 results on AEZS-112, which indicate the potential for safe combination with other anticancer drugs. We now look forward to working on the further development of AEZS-112 in collaboration with our expert investigators.”