Cambridge, UK, 2nd June 2010. Astex Therapeutics, the UK-based biotechnology company developing targeted therapies for oncology and virology, announced that interim data from an ongoing Phase I study of its novel HSP90 inhibitor, AT13387, is to be presented at the American Society of Clinical Oncology Annual Meeting, June 4-8, 2010, in Chicago, USA.
The Phase I study, in patients with refractory solid tumours, is being conducted at multiple sites in the US, with Dr Geoff Shapiro from the Dana-Farber Cancer Institute as Principal Investigator. The primary objective of the study is to determine the maximum tolerated dose of AT13387, with secondary objectives to investigate the safety and tolerability of the compound, its pharmacokinetic (PK) profile, and its pharmacodynamic (PD) activity in circulating blood cells and in tumours using PET scans and biopsies.
Interim clinical data, to be presented by Dr Shapiro, indicate that AT13387 is well tolerated, with no dose limiting toxicities observed at doses up to 120mg/m2/day. In addition, none of the hepatotoxicity seen with other compounds in this class has been observed in patients treated with AT13387. The data also demonstrate that AT13387 exhibits favourable PK and is associated with expected PD endpoints, including HSP70 up-regulation, in a dose dependent manner. Increases in caspase 3 in biopsy samples are indicative of induction of apoptosis in the tumour. The PD data demonstrate that the compound is achieving levels that are pharmacologically active in plasma and in tumour, consistent with the extended duration of action of the drug observed in preclinical testing. Stable disease has been observed in 24% of patients (5/21) for more than 2 cycles of treatment and in a further 10% of patients (2/21) for at least 6 months.
The Phase I study is designed to administer AT13387 as a one hour IV infusion, either once or twice weekly, for three weeks out of every four in patients with metastatic solid tumours, or with lymphoma, who are refractory to standard therapy. To date, a total of 26 patients have received AT13387 on a twice weekly schedule. Astex is currently planning for a Phase II study of AT13387 in patients with gastro-intestinal stromal tumours (GIST) to commence later this year and for a number of single agent and combination studies of AT13387 under its Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) that was entered into at the end of 2009.