ORLANDO, FL, USA (UroToday.com) - Data on a phase II trial of galeterone by Tokai Pharmaceuticals was presented on as a poster. Galeterone has a new mechanism of AR inhibition; it is able to induce degradation of AR without binding to the ligand binding domain (LBD) of the receptor. This novel mechanism might be especially useful in AR splice variant 7 (ARv7) which lacks the LBD and is associated with resistance to abiraterone and enzalutamide.
Patients treated in their phase II trial with treatment naïve metastatic prostate cancer had a 77% rate of > 50% PSA response; M0 and M1 treatment naïve patients had a 79% rate of > 50% PSA response. They substratified patients by presence of ARv7 and showed that there was an 88% rate of PSA decrease by > 50%. In preclinical models, galeterone results in near complete loss of AR and ARv7 in Western blot analysis.
On the heels of these data, the poster outlined the phase III trial design. Key inclusion criteria are progressive M1 disease on ADT, detectable ARv7 in circulating tumor cells (CTC) and ECOG status of 0 or 1. Prior treatment with abiraterone, enzalutamide, or chemotherapy excludes patients from the trial. They plan to accrue from 100 study sites in 9 countries and perform companion CTC diagnostic development.
Presented by Jennifer Roberts, Reena Dhillon, Daniel T. Dransfield, Khalid Kevin Mamlouk, and Karen J. Ferrante at the 2015 Genitourinary Cancers Symposium - "Integrating Biology Into Patient-Centric Care" - February 26 - 28, 2015 - Rosen Shingle Creek - Orlando, Florida USA
Tokai Pharmaceuticals, Cambridge, MA, USA
Reported by Phillip Abbosh, MD, PhD, medical writer for UroToday.com