Clinical activity and safety of ASN001, a selective CYP17 lyase inhibitor, administered without prednisone in men with metastatic castration-resistant prostate cancer (mCRPC).

240Background: ASN001 is a novel, non-steroidal, potent inhibitor of CYP17 lyase. It selectively inhibits synthesis of testosterone over cortisol in the adrenals to avoid the need for co-administration of prednisone. ASN001 also exhibits high oral bioavailability and low potential for drug-drug interaction supporting its use in future combination trials. Methods: This Phase 1/2 clinical trial in men with progressive mCRPC evaluates once-daily, oral ASN001 at escalating doses of 50, 100, 200, 300 and 400 mg (NCT02349139). While the Phase 1 also allowed enrollment of pretreated patients, no prior enzalutamide (ENZA) or abiraterone (ABI) is permitted in Phase 2. Endpoints included maximum dose (MTD) and dose limiting toxicities, recommended Phase 2 dose, pharmacokinetics, effect on steroid hormone biosynthesis and clinical efficacy (PSA and imaging). Results: To date, 23 mCRPC pts have been enrolled. No prednisone was administered and no mineralocorticoid excess has been reported. Overall, ASN001 was well to...