The primary objectives of this safety and tolerability study have been met. These were to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) for the compound when administered as a 24-hour intravenous infusion to patients with a diverse range of solid tumours on a three-weekly cycle.
”The conclusion of dose-escalation in this study is an important milestone in the development of CYT997”, said Mr Andrew Macdonald, Chief Executive Officer, “Planning for the compound’s future clinical program has been underway for sometime. We anticipate advancing the drug into Phase II clinical studies later this year”.
“Given the broad clinical potential for vascular-disrupting agents such as CYT997, we intend to investigate the activity of the compound in a range of cancer indications. Planning for both single-arm and randomised Phase II studies in combination with standard chemotherapies is currently being finalised.”
The company is also conducting a second Phase I dose-escalation study of CYT997 as an oral capsule formulation. This oral trial, which is partly funded under a $3.0m Commercial Ready grant, is being conducted at two locations in Queensland, Australia and is expected to conclude by December 2007.
Preliminary trial data
CYT997 was comparatively well tolerated in this study with the maximum tolerated dose in cancer patients (358 mg/m2) at least five-fold greater than doses tolerated in preclinical toxicology studies.
Two reversible dose-limiting toxicities were observed, namely a prolongation of the QTc interval (CTCAE Grade 3) and hypoxia/dyspnoea (shortness of breath; Grade 4). These toxicities were transient and were similar to those observed in Phase I studies for other vascular-disrupting agents.
Patients entering the trial had advanced cancer which had failed to respond to other therapies or for which no other therapy exists. Each was eligible to receive a maximum of six cycles of CYT997 therapy, subject to clinical status. A number of patients still remain on study and continue to receive the drug. Ongoing access to the drug under the Commonwealth Government’s Special Access Scheme (SAS) has been available to those patients who have completed the maximum number of dosing cycles.
Secondary objectives of the Phase I study included the determination of a recommended dose for Phase II studies; pharmacokinetic assessment and a preliminary investigation of the anti-tumour properties of the compound. Analysis of biological and clinical data from the study is currently ongoing and the company expects to present a finalised trial report, including a complete list of adverse events and the recommended dose for Phase II studies, within two months.
About Cytopia
Cytopia Ltd is an Australian biotechnology company focused on the discovery and development of new drugs to treat cancer and other diseases. Cytopia conducts its research and development via subsidiaries based in Melbourne and New York and specialises in discovering new molecules that can inhibit enzymes known as kinases, an exciting new class of drugs.
For more information our website at: www.cytopia.com.au
