CuraGen, TopoTarget begin clinical trial with PXD101 to treat tumors, lymphoma

By E. Janene Geiss

Philadelphia, March 29 - CuraGen Corp. and TopoTarget A/S announced Wednesday the start of patient dosing in a phase 1 clinical trial evaluating the safety and tolerability of PXD101, a small molecule histone deacetylase (HDAC) inhibitor, in combination with bortezomib (Velcade) for the treatment of patients with advanced malignancies, including solid tumors and lymphomas.

This trial is being sponsored by the National Cancer Institute under a clinical trials agreement with CuraGen for PXD101 and under a cooperative research and development agreement with Millennium Pharmaceuticals Inc. for bortezomib, according to a company news release.

National Cancer Institute-sponsored clinical trials with PXD101 are being conducted in parallel to those clinical trials sponsored by CuraGen, including the phase 1b/2 study of PXD101 plus Velcade (bortezomib) for the treatment of multiple myeloma initiated last week by CuraGen and TopoTarget, officials said.

This phase 1 trial is an open-label, dose-escalation study being led by 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 and safety profile of PXD101 in combination with bortezomib for patients with advanced solid tumors 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 maximum-tolerated dose, the study will enroll about 10 additional patients to further assess the biologic activity of PXD101 and bortezomib against tumor 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 1 study will build our knowledge and understanding of the safety and potential activity of the combination regimen, specifically for patients with refractory solid tumors or advanced lymphomas," Eckhardt, principal investigator, said in the release.

In preclinical in vitro studies, PXD101 monotherapy demonstrated growth-inhibitory activity against a variety of solid tumor types. And PXD101 monotherapy inhibited the growth of various hematological cancer cell lines, including lymphomas, at sub-micromolar potency and was highly active against cell lines that were resistant to other chemotherapeutics.

CuraGen is a Branford, Conn., biopharmaceutical company developing a pipeline of novel protein, antibody and small molecule therapeutics in the areas of oncology, inflammatory diseases and diabetes.

TopoTarget is a Copenhagen, Denmark, biopharmaceutical company dedicated to developing improved cancer therapies.

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