PCF-Funded Investigator Presents on Investigational Drug Galeterone
April 3, 2012 -- During the Clinical Trials Symposium at the 103rd AACR conference, PCF-funded investigator Mary-Ellen Taplin presented Phase I results of the investigational drug Galeterone (TOK-001) in chemotherapy naïve, hormone refractory metastatic prostate cancer patients. Galeterone has a three-pronged proposed mechanism of action, including:
1. Galeterone acts as an androgen receptor antagonist
2. Galeterone is a CYP17 lyase inhibitor
3. Galeterone effects androgen receptor degradation, which decreases androgen receptor levels
This trial was conducted in collaboration with Prostate Cancer Foundation supported investigator, Dr. Bruce Montgomery, through the Prostate Cancer Foundation—Department of Defense funded Prostate Cancer Clinical Trials Consortium (PCCTC). Of the 49 patients enrolled in the clinical trial, none had metastases. Dr. Taplin and colleagues observed a good safety and efficacy profile on this investigational drug in patients—with only one patient demonstrating serious adverse side effect, attributable to the investigational compound.
Galeterone showed great than 30% PSA reduction in all patients with some patients demonstrating 90% PSA declines. Tumor size reductions were also observed radiographically. A critical challenge for the agent in Phase II clinical trials is optimizing its bioavailability. In its current formulation, Galeterone is relatively insoluble and Dr. Taplin and colleagues are conducting drug formulation optimization. They plan to conduct a Phase IIA clinical trial in the second half of 2012 with the new formulation.
Prostate Cancer Foundation funded research; Dr. Johann DeBono provided a discussant on the trial at the Clinical Trials Symposium. DeBono suggested that though the compound has promising anti-hormone refractory metastatic properties demonstrating good evidence of radiological PSA decline, the pharmacokinetic-pharmacodynamic data in the trial were insufficient. Dr. DeBono also addressed pertinent questions regarding Galeterone mechanism of action, in terms of androgen receptor degradation and blocking CYP17in the Abiraterone and MDV3100 resistant setting.