Reference Detail

Ref Type

Journal Article

PMID

(32327394)

Authors

Madan RA, Schmidt KT, Karzai F, Peer CJ, Cordes LM, Chau CH, Steinberg SM, Owens H, Eisner J, Moore WR, Dahut WL, Gulley JL, Figg WD

Title

Phase 2 Study of Seviteronel (INO-464) in Patients With Metastatic Castration-Resistant Prostate Cancer After Enzalutamide Treatment.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical genitourinary cancer			2020 Mar 29	258-267.e1	Clin Genitourin Cancer

URL

Abstract Text

Seviteronel was being developed by Innocrin Pharmaceuticals as a selective cytochrome P450c17a (CYP17) 17,20-lyase (lyase) inhibitor and androgen receptor antagonist with activity against prostate cancer cells in vitro and in vivo. This open-label phase 2 clinical study evaluated the tolerability and efficacy of seviteronel in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with enzalutamide.Patients with mCRPC whose disease previously progressed while receiving enzalutamide therapy were divided into 2 cohorts on the basis of prior exposure to docetaxel. Seviteronel was administered without routine oral steroids either twice daily with dose titration (450 mg) or once daily without dose titration (600 or 750 mg). The primary objective was to determine the rate of significant prostate-specific antigen response (ie, decline of ≥ 50%) after 12 weeks of seviteronel therapy.Seventeen patients, with a median (range) age of 71 (60-92) years, were enrolled, with 8 patients having received prior docetaxel. Patients received a median of 2 cycles of treatment, with most patients discontinuing treatment because of toxicity related to the study drug. The most common adverse events included concentration impairment, fatigue, tremor, and nausea. Despite changes in dosing, the study was closed prematurely because of the high magnitude of toxicity. One (6%) of 17 patients experienced a significant decline in prostate-specific antigen.Seviteronel was not generally well tolerated nor associated with significant clinical responses in patients with mCRPC who had previously received enzalutamide. Further investigation of single-agent seviteronel in this patient population is not warranted; however, studies investigating seviteronel with low-dose dexamethasone are ongoing in patients with androgen receptor-positive tumors.

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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