Clinical Activity And Safety Of Asn001, A Selective Cyp17 Lyase Inhibitor, Administered Without Prednisone In Men With Metastatic Castration-Resistant Prostate Cancer (Mcrpc): A Phase 1/2 Clinical Trial.

5041 Background: ASN001 is a novel, non-steroidal, potent inhibitor of CYP17 lyase that 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. Methods: This Phase (Ph) 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 Ph 1 also allowed enrollment of pretreated patients, no prior enzalutamide (ENZA) or abiraterone (ABI) is permitted in Ph 2. Endpoints include maximum dose (MTD) and dose limiting toxicities, recommended Ph 2 dose, PK, effect on steroid hormone biosynthesis and clinical efficacy (PSA and imaging). Results: To date, 26 mCRPC pts have been enrolled. No prednisone was administered and no mineralocorticoid excess has been reported. Overall, ASN001 was well tolerated. Most drug-related adverse events were Gr 1/2 and included fatigue, constipation and nausea. At 400mg, two pts experienced asymptomatic, reversible Gr 3 ALT/AST elevation, but no recurrence when retreated at 300mg. Enrollment of ABI/ENZA naïve patients continues at lower doses to further evaluate safety and efficacy. Testosterone decrease to below quantifiable limits and DHEA decrease of up to 80% was observed. Systemic exposure was high (C max , AUC and T 1/2 at 300 mg QD were 6.7 µM, 80 µM.h and 21.5 h, respectively). Stable disease up to 18+ months has been observed despite prior ABI and ENZA exposure. PSA decline of > 50% (up to 93% decline) and up to 37+ wks duration was observed in 3 of 4 ABI/ENZA naïve patients at starting doses of 300/400mg. Conclusions: Overall, ASN001 was safe and well tolerated. Prednisone co-administration was not needed. Encouraging preliminary evidence of efficacy is reflected by PSA declines in evaluable mCRPC pts not pretreated with ABI or ENZA and by durable disease stabilization in refractory disease. Enrollment is ongoing at doses below 400mg QD in ABI/ENZA naïve mCRPC pts. Updated and detailed results will be presented at the meeting. Clinical trial information: NCT02349139.