Tokai Pharmaceuticals (United States)

4665 Background: Galeterone is an oral steroid analog that suppresses prostate cancer growth by inhibiting CYP17, blocking androgen receptor and reducing androgen receptor levels. Methods: Open label, multicenter dose-finding study assessing the safety, pharmacokinetics and clinical effect of escalating doses of galeterone in chemotherapy naïve CRPC patients (pts). Pts were enrolled in cohorts from 650-2,600mg of galeterone daily for 12 wks. Study also explored effects of food supplement and scheduling. Pts remained on study until disease progression or dose limiting toxicity. Results: Pt characteristics included median age 69 (47-92), median PSA 24 (6-200), and 46.9% with metastases. 36 of 49 pts completed 12 wks of study with early discontinuation for toxicity (6), progression (5), or withdrawal of consent (2). Maximal tolerated dose was not reached. The frequency of AEs was 58% grade 1, 30% grade 2, 8% grade 3 and 1% grade 4. Transient LFT elevations were seen in 15 men (5 with suspected or confirmed Gilberts). There was no trend for increasing toxicity with dose escalation and no PK difference in Gilberts pts. 9 SAEs were reported with one considered related to galeterone (rhabdomyolysis with acute renal failure in the context of high dose statin use). Overall 11/49 pts (22%) demonstrated >50% PSA decline and an additional 13/49 (26%) had 30-50% declines. Partial response by RECIST was seen in 2 pts. Consistent with lyase inhibition, increased corticosteroids and suppressed androgens were seen with dose escalation. Analysis of limited plasma collected 4 - 30 hours after dosing showed high interpatient variability with no consistent relationship to dose or time after dosing. Conclusions: Galeterone was well tolerated in CRPC pts and demonstrated clinical activity. Galeterone is being reformulated with additional PK and phase II trials planned. [Table: see text]