Oncology-focused drug development company Curis has initiated a Phase I dose-escalation study of CUDC-427, an oral, synthetic, small molecule that triggers tumour cell apoptosis, in advanced malignancies.
The first patient was dosed in the open-label, multicentre study currently being conducted using a continuous, twice-daily oral dosing regimen in patients with advanced and refractory solid tumours or lymphoma.
Curis president and chief operating officer Ali Fattaey said that using a continuous daily dosing regimen CUDC-427 monotherapy has the potential to further enhance its anti-tumour activity as a single agent in difficult to treat cancers.
"The expansion phase of this trial will further study CUDC-427's activity in patients with ovarian and fallopian tube cancers, where we expect to investigate CUDC-427 in patients with cancers of different genetic profiles, including patients with known gene mutations," Fattaey said.
The primary objectives are to assess the maximum tolerated dose (MTD) and recommended Phase II dose of CUDC-427 using a more frequent dosing regimen.
Safety and tolerability, pharmacokinetics, exploratory biomarkers of activity and preliminary anti-cancer activity of CUDC-427 form the secondary objectives.
Beginning with 400mg/day (200mg BID) and escalated at increments of 200mg/day, patients will be dosed according to the standard 3+3 design.
On determination of MTD or the recommended Phase II dose, an expansion cohort of the trial will enrol around 12 patients primarily to include ovarian and fallopian tube cancers.
Image: Lymph node with mantle cell lymphoma. By immunohistochemistry the lymphoma cells expressed CD5, CD20 and Cyclin D1. Photo: courtesy of Gabriel Caponetti.