CuraGen and TopoTarget Initiate Phase Ib/II Clinical Trial with PXD101 and Velcade(R) for Multiple Myeloma

24-Mar-2006

CuraGen Corporation and TopoTarget A/S announced the initiation of patient dosing in a Phase Ib/II proof-of-concept trial to evaluate PXD101, a small molecule histone deacetylase (HDAC) inhibitor, in combination with Velcade(R) (bortezomib) for the treatment of relapsed, refractory multiple myeloma, a deadly form of blood cancer. Preliminary results from this open-label, multi-center study are expected by mid-2007.

The goal of the Phase Ib portion of this trial is to establish the maximum tolerated dose (MTD) of PXD101 in combination with Velcade(R) in up to 30 patients who have failed at least two prior lines of therapy for multiple myeloma. Following determination of the MTD, the study will enter Phase II and enroll up to 15 additional patients with relapsed, refractory multiple myeloma who have failed at least one prior therapy. The Phase II portion of the study will further evaluate the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of PXD101 in combination with Velcade(R). Patients will be enrolled at multiple sites in the United States.

In vitro studies published in the literature have shown that HDAC inhibitors and Velcade(R) act through independent mechanisms that lead to enhanced killing of multiple myeloma cells when combined. In preclinical studies, PXD101 demonstrated growth-inhibitory activity against a variety of multiple myeloma cell lines at nanomolar concentrations. PXD101 also showed synergistic activity when combined with Velcade(R) against multiple myeloma during in vitro studies. These data support the evaluation of PXD101 in combination with Velcade(R) for the treatment of multiple

PXD101 is a small molecule HDAC inhibitor being investigated for its role in the treatment of a wide range of solid and hematologic malignancies either as a single-agent, or in combination with other active anti-cancer agents. HDAC inhibitors represent a new mechanistic class of anti-cancer therapeutics that target HDAC enzymes and have been shown to: arrest growth of cancer cells (including drug resistant subtypes); induce apoptosis, or programmed cell death; promote differentiation; inhibit angiogenesis; and sensitize cancer cells to overcome drug resistance when used in combination with other anti-cancer agents.

https://www.bionity.com/en/news/53388/curagen-and-topotarget-initiate-phase-ib-ii-clinical-trial-with-pxd101-and-velcade-r-for-multiple-myeloma.html