Introduction: Galeterone is an orally available, semi-synthetic steroid analog for the treatment of castration-resistant prostate cancer (CRPC) that inhibits prostate cancer growth through a triple mechanism-of-action by: a) inhibiting CYP17 lyase activity; b) binding to and inhibiting the androgen receptor; and, c) degrading androgen receptor protein. ARMOR1, a phase I dose escalation study in men with chemotherapy naive CPRC, evaluated the safety of galeterone. Preliminary efficacy was also assessed by measuring changes in prostate-specific antigen (PSA) levels and tumor response. Methods: Forty-nine men with metastatic and non-metastatic chemotherapy-naïve CRPC were enrolled in the ARMOR1 study. Patients were enrolled with confirmed adenocarcinoma of the prostate and disease progression during androgen ablation therapy. Patients ranged in age from 48 to 93 years old and had ECOG status of 0 or 1. Patients were randomized to one of eight dose escalation cohorts receiving galeterone capsules in single or split oral doses of 650, 975, 1300, 1950, or 2600mg daily for 12 weeks. After 12 weeks, eligible patients could continue treatment in an extension phase. Results: Maximum tolerated dose was not reached. The frequency of patients with Grade 1 and Grade 2 adverse events (AEs) reported by body system was 58% and 30% respectively. The most commonly reported AEs by patient were fatigue (36.7%), aspartate aminotransferase (AST) increase (32.7%), alanine aminotransferase (ALT) increase (30.6%), nausea (28.6%), diarrhea (26.5%), and pruritus (24.5%). Grade 2 and 3, transient, non-serious, elevations of liver function tests (LFTs) were observed in 15 patients with the majority being completely asymptomatic. Of these patients, 11 underwent drug interruptions, and 6 of 7 patients were successfully rechallenged and returned to treatment with no recurring Grade 3 or higher LFT elevations. Nine SAEs were reported in the study, with all except one unrelated to galeterone. The single, related, grade 4 case involved rhabdomyolysis that occurred in the setting of simvastatin therapy (40 mg qd) and underlying renal insufficiency. No events of adrenal mineralocorticoid excess (AME) were observed in this study. PSA reductions were seen in a majority of patients; 24 (49%) patients had >30% maximal PSA reductions, including 11 patients (22%) with >50% maximal PSA reductions. Conclusion: Galeterone was well tolerated, with all cohorts showing an acceptable safety profile. Galeterone also demonstrated activity in patients with CRPC. Additional long term safety will be further explored in a planned phase II study.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr CT-07. doi:1538-7445.AM2012-CT-07