MP27-15: Sabizabulin has both cytotoxic and cytostatic activity in Phase 1b/2 clinical of men with metastatic castration resistant prostate cancer who progressed on androgen receptor targeting agents

Mark Markowski*, Mario Eisenberger, Baltimore, MD, Christopher Pieczonka, Syracuse, NY, Robert Getzenberg, Domingo Rodriguez, K. Gary Barnette, MItchell Steiner, Miami, FL, Daniel Saltzstein, San Antonio, TX, Emmanuel Antonarakis, Baltimore, MD, Ronald Tutrone, Towson, MD

Introduction: 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 (ARTAs).

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 (RP2D) of 63 mg daily.  Based upon the Phase 1b/2 data, sabizabulin appears to have both cytotoxic and cytostatic activity.  A analysis was conducted evaluating the best clinical response (BCR) defined as either an objective response assessed by PCWG3 criteria and/or stable disease defined as > 5 cycles (> 15 weeks) of continuous treatment.

Results: Of the combined 80 patients in the Phase 1b/2 portions of the study, the BCR was 37.5% (30/80) and 5 of the responders remain on study with the longest being treated for more than 30 months.  Of the patients with measurable disease at study entry, the BCR was 59% (17/29). Prior to study entry, 11/30 (37%) of those with a BCR had previously been treated with and subsequently progressed on a minimum of 2 ARTAs.  The remaining 19/30 (63%) had progressed on a single ARTA agent.  11 (37%) were previously treated with enzalutamide or apalutamide and 8 (27%) with abiraterone as single agents.  8 (27%) received enzalutamide and abiraterone and 3 (10%) patients received more than two ARTAs.  As described previously, the safety profile continues to be favorable with no clinically relevant neutropenia or neurotoxicity and the most commonly observed adverse events being gastrointestinal in nature.

Conclusions: In this analysis, sabizabulin has demonstrated not only cytotoxic, but also significant cytostatic activity with similar responses in men that have progressed on a single or multiple ARTA agents.  Sabizabulin is a novel agent with the potential provide men with mCRPC a well-tolerated chronic treatment cytostatic option after progressing on an ARTA and is being tested in the open Phase 3 VERACITY trial.

Source of Funding: Veru Inc.