Related Experiment Video
Updated: Feb 7, 2026
07:25
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
13.9K
Phase I Study of Seviteronel, a Selective CYP17 Lyase and Androgen Receptor Inhibitor, in Men with
Shilpa Gupta1, Luke T Nordquist2, Mark T Fleming3
1University of Minnesota, Minneapolis, Minnesota. nshore@gsuro.com guptash@umn.edu.
Summary
Seviteronel is a well-tolerated prostate cancer drug. The Phase I study found 600 mg daily to be the recommended dose for future castration-resistant prostate cancer trials.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Castration-resistant prostate cancer (CRPC) remains a significant clinical challenge.
- Selective androgen receptor (AR) and cytochrome P450c17a (CYP17) inhibitors offer novel therapeutic strategies.
- Seviteronel (INO-464) demonstrates preclinical antitumor activity.
Purpose of the Study:
- To evaluate the safety, tolerability, pharmacokinetics, and activity of seviteronel in male patients with CRPC.
- To determine the recommended Phase II dose for seviteronel in CRPC.
Main Methods:
- Open-label, Phase I clinical study.
- Seviteronel administered orally once daily at doses of 600 mg (with dose titration) and 600, 750, 900 mg (without dose titration).
- Primary objectives: safety, tolerability, and maximum tolerated dose (MTD).
- Secondary objectives: pharmacokinetics, PSA response, tumor response, and endocrine effects.
Main Results:
- Twenty-one chemotherapy-naïve CRPC subjects were enrolled.
- No dose-limiting toxicities (DLT) were observed up to 750 mg once daily.
- Most treatment-emergent adverse events (AE) were Grade 1-2, commonly fatigue, dizziness, blurred vision, and dysgeusia.
- Adverse events generally improved with dose modification.
Conclusions:
- Once-daily seviteronel was generally well tolerated in men with CRPC, including those with prior abiraterone acetate or enzalutamide treatment.
- 600 mg once daily was identified as the recommended Phase II dose.
- Seviteronel shows promise as a treatment option for CRPC.
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