Tokai Pharmaceuticals said today it will terminate the Phase III ARMOR3-SV trial comparing its lead candidate galeterone to Xtandi® (enzalutamide) in treatment-naïve metastatic castration-resistant prostate cancer (mCRPC) patients whose prostate tumors express androgen receptor splice variant-7 mRNA (AR-V7).
Tokai said it was following a recommendation of the trial’s independent Data Monitoring Committee, which has concluded that ARMOR3-SV trial is unlikely to meet its primary endpoint of demonstrating improved radiographic progression-free survival (rPFS) for galeterone versus enzalutamide in AR-V7-positive mCRPC.
Galeterone is an oral small molecule that utilizes the mechanistic pathways of current second-generation hormonal therapies, including abiraterone and enzalutamide, while also introducing a unique third mechanism—androgen receptor degradation—that impairs the function of androgen receptors, decreasing their sensitivity to androgen activity and reducing tumor growth. Tokai is developing galeterone for the treatment of patients with metastatic castration-resistant prostate cancer. Tokai has worldwide development and commercialization rights to galeterone.
The DMC did not cite any safety concerns with galeterone in the trial, Tokai added. The company plans to present data from the trial at an unspecified scientific forum once it is available and has been analyzed.
“We are very disappointed by this outcome. An immediate priority is to analyze the unblinded study data in detail as we evaluate potential paths forward for galeterone and our pipeline,” Tokai President and CEO Jodie Morrison said in a statement.
Tokai has global development and commercialization rights to galeterone, an oral small molecule being developed for treating patients with mCRPC. Galeterone uses the mechanistic pathways of current second-generation hormonal therapies, including abiraterone and enzalutamide, while also introducing a unique third mechanism, androgen receptor degradation, which is designed to impair the function of androgen receptors, decreasing their sensitivity to androgen activity and reducing tumor growth.
ARMOR3-SV was designed to compare galeterone to enzalutamide in mCRPC treatment-naïve patients whose prostate tumors express the AR-V7 splice variant. The trial selected patients with the variant by using an AR-V7 clinical trial assay successfully optimized for global use by Qiagen.
Tokai said it also intends to evaluate its ongoing expansion of the ARMOR2 trial in mCRPC patients with acquired resistance to enzalutamide, as well as a planned study in patients who rapidly progress on either enzalutamide or abiraterone acetate.
All patients currently enrolled in the ARMOR2 and ARMOR3-SV trials will be allowed to continue on therapy following consultation with their physicians and study investigators, Tokai said.