Tokai to move TOK-001 (galeterone) into Phase II trials later in year

According to a media release issued on Saturday by Tokai Pharmaceuticals, their investigational agent galeterone (TOK-001) “was well-tolerated with minimal side effects and demonstrated efficacy” in a Phase I clinical trial among men with metastatic, castration-resistant prostate cancer (mCRPC). The company has stated that an initial Phase II trial of galeterone will be initiated some time later this year.

The full paper by Taplin et al. will be presented at the upcoming meeting of the American Association of Cancer Research (AACR) in Chicago, a little after 2:00 pm Eastern time on Tuesday, April 3rd. The abstract of the presentation has been embargoed until that time. In the interim, here is a summary of what we know now:

  • The primary goals of the study was to assess the impact of galeterone therapy on patients’ PSA levels and the safety of galeterone in clinical practice.
  • The trial enrolled 49 men with mCRPC who received a series of escalating doses of galeterone over time.
  • 11/49 patients (22 percent) had reductions in their PSA levels of 50 percent or more.
  • An additional 13/49 patients (27 percent) had reductions in their PSA levels of 30 to 49 percent.
  • CT scans showed significant reductions in tumor size among some patients.
  • Side effects were generally minor, including fatigue, nausea and diarrhea.
  • Transient elevations in liver function tests were observed in 15/49 patients (31 percent).
    • The majority of these patients had no related symptoms.
    • 11/15 patients stopped galeterone treatment.
    • 7/11 patients were re-challenged with galeterone.
    • 6/7 patient re-challenged were successfully returned to treatment with no significant recurrence of liver function test elevations.

Galeterone is an oral drug that is said to disrupt the growth and survival of prostate cancer cells by combining three different mechanisms of action. Supposedly it can act as an androgen receptor antagonist, as a CYP17 lyase inhibitor, and by lowering androgen receptor levels in prostate tumors. More information about the mechanism of action of galeterone is available on the company web site.

From the trial summary on the web site, we do know that patients in this trial could not have received prior treatment with any of the following drugs: ketoconazole, MDV3100, abiraterone, sipuleucel-T, or TAK700. They also had to be chemotherapy-naive (i.e., not treated with either docetaxel- or carbazitaxel-based chemotherapy or with mitoxantrone). We also know that the total daily dose of galeterone was scheduled start at 650 mg/day and be escalated to as high as 2,600 mg/day.

The occurrence of significant elevations in liver function tests in this Phase I trial does suggest that, however effective galeterone may prove to be, regular monitoring of liver function enzyme activity would be needed in men treated with this drug. It appears that 5/49 patients (10 percent) were unable to stay on galeterone treatment after a some dose level of the drug.

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