PURPOSE
Sabizabulin, an oral cytoskeleton disruptor was tested in a Phase 1b/2 clinical study in men with metastatic castration resistant prostate cancer (mCRPC).
EXPERIMENTAL DESIGN
The Phase 1b portion utilized a 3+3 design with escalating daily oral doses of 4.5 mg - 81 mg and increasing schedule in 39 mCRPC patients treated with one or more androgen receptor targeting agents. Prior taxane chemotherapy was allowed. The Phase 2 portion tested a daily dose of 63 mg in 41 patients with no prior chemotherapy. Efficacy was assessed using PCWG3 and RECIST 1.1 criteria.
RESULTS
The MTD was not defined in the Phase 1b and the recommended Phase 2 dose was set at 63 mg/day. The most common adverse events (>10% frequency) at the 63 mg oral daily dosing (combined Phase 1b/2 data) were predominantly Grade 1-2 events. Grade ³3 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 {greater than or equal to}1 continuous cycle of 63 mg or higher included objective response rate in 6/29 (20.7%) patients with measurable disease (1 complete, 5 partial) and 14/48 (29.2%) patients had PSA declines. The Kaplan-Meier median radiographic progression-free survival was estimated to be 11.4 months (n=55). Durable responses lasting >2.75 years were observed.
CONCLUSIONS
This clinical trial demonstrated that chronic oral daily dosing of sabizabulin has a favorable safety profile with preliminary antitumor activity. These data support the ongoing Phase 3 VERACITY trial of sabizabulin in men with mCRPC.