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Published on: March 6, 2018
Androgen Receptor Modulation Optimized for Response (ARMOR) Phase I and II Studies: Galeterone for the Treatment of
Bruce Montgomery1, Mario A Eisenberger2, Matthew B Rettig3
1University of Washington, Seattle, Washington.
Purpose:
Galeterone is a selective, multitargeted agent that inhibits CYP17, antagonizes the androgen receptor (AR), and reduces AR expression in prostate cancer cells by causing an increase in AR protein degradation. These open-label phase I and II studies [Androgen Receptor Modulation Optimized for Response-1 (ARMOR1) and ARMOR2 part 1] evaluated the efficacy and safety of galeterone in patients with treatment-naive nonmetastatic or metastatic castration-resistant prostate cancer (CRPC) and established a dose for further study.
Experimental Design:
In ARMOR1, 49 patients received increasing doses (650-2,600 mg) of galeterone in capsule formulation; 28 patients in ARMOR2 part 1 received increasing doses (1,700-3,400 mg) of galeterone in tablet formulation for 12 weeks. Patients were evaluated biweekly for safety and efficacy, and pharmacokinetic parameters were assessed.
Results:
In ARMOR1, across all doses, 49.0% (24/49) achieved a ≥30% decline in prostate-specific antigen (PSA; PSA30) and 22.4% (11/49) demonstrated a ≥50% PSA decline (PSA50). In ARMOR2 part 1, across all doses, PSA30 was 64.0% (16/25) and PSA50 was 48.0% (12/25). In the 2,550-mg dose cohort, PSA30 was 72.7% (8/11) and PSA50 was 54.5% (6/11). Galeterone was well tolerated; the most common adverse events were fatigue, increased liver enzymes, gastrointestinal events, and pruritus. Most were mild or moderate in severity and required no action and there were no apparent mineralocorticoid excess (AME) events.
Conclusions:
The efficacy and safety from ARMOR1 and ARMOR2 part 1 and the pharmacokinetic results support the galeterone tablet dose of 2,550 mg/d for further study. Galeterone was well tolerated and demonstrated pharmacodynamic changes consistent with its selective, multifunctional AR signaling inhibition.
Insights
Galeterone showed promising efficacy in treating prostate cancer by reducing prostate-specific antigen (PSA) levels. This agent was well-tolerated, supporting further clinical investigation for castration-resistant prostate cancer (CRPC).
Area of Science:
- Oncology
- Pharmacology
Background:
- Galeterone is a novel agent targeting CYP17 and the androgen receptor (AR).
- It inhibits AR signaling and reduces AR expression in prostate cancer cells.
- Previous studies established its mechanism of action in preclinical models.
Purpose of the Study:
- To evaluate the efficacy and safety of galeterone in patients with treatment-naive nonmetastatic or metastatic castration-resistant prostate cancer (CRPC).
- To establish an optimal dose for further clinical studies.
- To assess pharmacokinetic parameters of galeterone formulations.
Main Methods:
- Open-label Phase I/II studies (ARMOR1 and ARMOR2 part 1) were conducted.
- Patients received escalating doses of galeterone in capsule or tablet formulations.
- Safety, efficacy (PSA decline), and pharmacokinetics were assessed biweekly over 12 weeks.
Main Results:
- In ARMOR1, 49.0% of patients achieved a ≥30% PSA decline (PSA30).
- In ARMOR2 part 1, 64.0% achieved PSA30 and 48.0% achieved a ≥50% PSA decline (PSA50).
- The 2,550-mg tablet dose showed 72.7% PSA30 and 54.5% PSA50; galeterone was well-tolerated with manageable adverse events and no mineralocorticoid excess.
Conclusions:
- The galeterone tablet dose of 2,550 mg/d is supported by efficacy, safety, and pharmacokinetic data.
- Galeterone demonstrated pharmacodynamic effects consistent with its mechanism of action.
- Further studies are warranted to confirm these findings in a larger patient population.
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