Abstract 1387P
Background
Sabizabulin is a novel oral cytoskeleton disruptor being developed for use in metastatic castration-resistant prostate cancer (mCRPC). A phase 1b/2 clinical study was conducted to establish the maximum tolerated dose (MTD) and evaluate the preliminary efficacy in men with mCRPC resistant to androgen receptor targeting agents.
Methods
The phase 1b portion of the study in 39 men utilized escalating and expanding dose and duration. The phase 2 portion studied 41 men with mCRPC at the recommended phase 2 dose of 63 mg daily. Efficacy was assessed by bone/CT scans. A final analysis of the safety and efficacy data including the primary endpoint, the median progression-free survival, was conducted.
Results
Although the MTD was not reached in the phase 1b, the recommended phase 2 dose was set at 63 mg/day to maximize GI tolerability. The most common adverse events (>10% frequency) at the 63 mg oral daily dosing (combined phase 1b/2 data) were predominantly Grade 1-2. Grade ≥3 events included diarrhea (7.4%), fatigue (5.6%) and ALT/AST elevations (5.6% and 3.7%, respectively). Neurotoxicity and neutropenia were not observed. Preliminary efficacy data in patients treated with ≥1 continuous cycle (21 days) of 63 mg or higher (n=55) included an objective response rate of 6/29 (20.7%) in patients with measurable disease (1 complete, 5 partial). 14/48 (29.2%) of the patients had PSA declines. The Kaplan-Meier median radiographic progression-free survival was estimated to be 11.4 months (95% C.I. 29.63-65.79) (n=55). Durable responses lasting >2.75 years were observed with 14.5% (8/55) demonstrating a response greater than 12 months.
Conclusions
This clinical trial demonstrated that chronic oral daily dosing of sabizabulin has a favorable safety profile with significant preliminary cytotoxic and cytostatic antitumor activity. These data support the ongoing phase 3 VERACITY trial of sabizabulin in men with mCRPC who have progressed on an androgen receptor targeting agent.
Clinical trial identification
NCT03752099.
Editorial acknowledgement
Legal entity responsible for the study
Veru Inc.
Funding
Veru Inc.
Disclosure
M. Eisenberger, D. Rodriguez, K.G. Barnette, R.H. Getzenberg, M.S. Steiner: Financial Interests, Personal, Member of the Board of Directors: Veru Inc. D.R. Saltzstein, R.F. Tutrone: Financial Interests, Personal, Advisory Role: Veru Inc. All other authors have declared no conflicts of interest.