TopoTarget and CuraGen announce initiation of first NCI-sponsored clinical trial with PXD101

TopoTarget A/S (CSE: TOPO) and CuraGen Corp. (Nasdaq: CRGN) announce the initiation of patient dosing in a new Phase I trial with their small molecule histone deacetylase (HDAC) inhibitor, PXD101.

The trial is the first PXD101 study to be sponsored by the US National Cancer Institute (NCI) and will evaluate the safety and tolerability of PXD101 in combination with bortezomib (Velcade®) for the treatment of patients with advanced malignancies, including solid tumours and lymphomas. NCI-sponsored clinical trials with PXD101 are being conducted in parallel to those clinical trials sponsored by CuraGen, including the Phase Ib/II study of PXD101 plus Velcade® for the treatment of multiple myeloma initiated last week by TopoTarget and CuraGen.

This Phase I trial is an open-label, dose-escalation study being led by Dr. S. Gail Eckhardt, Director of the Developmental Therapeutics and GI Malignancies Programs and Professor of Medicine at the University of Colorado Health Sciences Center. The study aims to establish the maximum tolerated dose (MTD) and the safety profile of PXD101 in combination with bortezomib (Velcade®), a proteasome inhibitor for patients with advanced solid tumours or lymphomas, which are refractory to standard therapies or for which no standard treatment exists. Up to 36 patients will be enrolled in the dose escalation portion of the study and receive PXD101 and bortezomib in a three week cycle. Following determination of the MTD, the study will enrol approximately ten additional patients to further assess the biologic activity of PXD101 and bortezomib against tumour cells, including inhibition of HDAC and the proteasome.

“Based on the reported preclinical findings for PXD101 and bortezomib, these compounds appear to work through distinct pathways that are complementary to one another, and when combined, demonstrate synergistic activity against certain cancers in vitro. This Phase I study will build our knowledge and understanding of the safety and potential activity of the combination regimen, specifically for patients with refractory solid tumours or advanced lymphomas,” stated Dr. Eckhardt, Principal Investigator.

In preclinical in vitro studies, PXD101 has demonstrated growth-inhibitory activity against a variety of solid tumour types. Furthermore, PXD101 monotherapy has inhibited the growth of various haematological cancer cell lines, including lymphomas, at sub-micromolar potency and was highly active against cell lines that were resistant to other chemotherapeutics. Preclinical studies evaluating the combination of HDAC inhibitors and bortezomib have been reported in the literature and indicate synergistic anti-cancer activity against solid tumour and haematologic cancer cell lines.

Peter Buhl Jensen, CEO of TopoTarget stated:

‘We believe that the PXD101/bortezomib combination appears promising in the fight against cancer. This NCI study complements our in-house trial and will give us a broader understanding of the activity and potential of this intriguing combination therapy.’

The trial is being sponsored by the NCI under a Clinical Trials Agreement with CuraGen for PXD101 and under a Cooperative Research and Development Agreement (CRADA) with Millennium Pharmaceuticals Inc. for bortezomib.