Reference Detail

Ref Type

Journal Article

PMID

(30012563)

Authors

Gupta S, Nordquist LT, Fleming MT, Berry WR, Zhang J, Ervin SL, Eisner JR, Baskin-Bey ES, Shore ND

Title

Phase I Study of Seviteronel, a Selective CYP17 Lyase and Androgen Receptor Inhibitor, in Men with Castration-Resistant Prostate Cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	24	21	2018 11 01	5225-5232	Clin Cancer Res

URL

Abstract Text

Purpose: Seviteronel (INO-464) is a selective cytochrome P450c17a (CYP17) 17,20-lyase (lyase) and androgen receptor (AR) inhibitor with antitumor activity in vitro and in vivo This open-label phase I clinical study evaluated the safety, tolerability, pharmacokinetics and activity of once-daily seviteronel in male chemotherapy-naïve subjects with castration-resistant prostate cancer (CRPC).Patients and Methods: Seviteronel was administered at 600 mg once daily with dose titration (DT) and in modified 3 + 3 dose escalation once-daily cohorts at 600, 750, and 900 mg without DT. The primary objectives of this study were to establish safety, tolerability, and the MTD of seviteronel in chemotherapy-naïve subjects with or without prior treatment with FDA-approved CRPC treatments, abiraterone acetate (AA), and enzalutamide. Secondary objectives were to assess pharmacokinetics, PSA, tumor response, and endocrine results.Results: Twenty-one subjects were enrolled. No dose-limiting toxicities (DLT) were observed through 750 mg once daily. Most treatment-emergent adverse events (AE) reported at grade 1-2. The most commonly reported AEs were fatigue (71%), dizziness (52%), blurred vision (38%), and dysgeusia (33%), with most AEs improving after dose reduction or dose interruption.Conclusions: Once-daily seviteronel was generally well tolerated in this phase I study of men with CRPC, a majority of which had progressed on prior AA or enzalutamide, or both. Of the doses evaluated, 600 mg once daily was chosen as the recommended phase II dose for future studies in subjects with CRPC. Clin Cancer Res; 24(21); 5225-32. ©2018 AACR.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Seviteronel	Seviteronel	0	1

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Seviteronel		VT-464\|INO-464	Hormone - Anti-androgens 48	Seviteronel (VT-464) is a small molecule inhibitor of CYP17 17,20 lyase activity, resulting in decreased androgen production, which may inhibit growth of androgen-dependent tumors (PMID: 30012563, PMID: 25351916, PMID: 32327394).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References