615MO - Phase Ib/II study of VERU-111, novel, oral tubulin inhibitor, in men with metastatic castration resistant prostate cancer (mCRPC) who failed an androgen blocking agent

Background

VERU-111 is an oral, a & b tubulin inhibitor of microtubule polymerization with no affinity for multidrug resistance proteins. A phase 1b/2 clinical study is being conducted to establish the maximum tolerated dose (MTD) and evaluate the preliminary efficacy in men with progressive mCRPC resistant to androgen blocking agents +/- a taxane.

Methods

Phase 1b study was a 3x3 design with escalating oral dosing of 4.5 mg to 81 mg (7 days on drug/14 days off per 21 day cycle). After no dose limiting toxicity was observed, the dose was increased in the next cohort. The schedule was also expanded in those completing the 7 days on/14 days off cycle to continuous dosing/cycle.

Results

30 taxane-naïve mCRPC men with a median age of 76 (61-92) were enrolled. 8 received prior enzalutamide, 12 abiraterone and 10 both. 8 men had bone mets, 5 lymph node, 5 mixed and 1 had soft tissue metastases. The MTD of VERU-111 is 72mg (3 /11 men had Grade 3 diarrhea). No Grade 3 diarrhea was observed at doses <72 mg per day. At doses < 72mg/d, the most common AEs were mild to moderate nausea, vomiting, diarrhea, and fatigue, with no observed neurotoxicity or neutropenia. Antitumor activity was assessed by PSA and bone/CT scans in men that were treated for ≥ 4 continuous 21-day cycles. 5/8 (63%) had PSA declines: 4 (50%) men had ≥ 30% and 2(25%) ≥ 50% declines compared to their 21 day cycle baseline. Based on PCWG3/RECIST 1.1 criteria, objective tumor responses were seen in 2 men (soft tissue and bone) and 5/8 (63%) had stable disease. Objective responses and PSA declines lasted > 12 weeks. Median duration of response has not been reached as 7/8 of the men are still being treated on study with a current duration of 10 months (6-15 months) and three additional men have not yet completed ≥ 4 continuous 21-day cycles.

Conclusions

The phase 1b portion demonstrates that oral VERU-111 has a favorable safety profile allowing for chronic administration and significant/durable antitumor activity. The daily dose of 63mg is being tested in the phase 2 portion. Oral administration, safe long-term treatment and evidence of antitumor activity highlight a potential prominent role of VERU 111 for the treatment of men with mCRPC who failed an androgen blocking agent.

Clinical trial identification

NCT03752099.

Editorial acknowledgement

Legal entity responsible for the study

Veru Inc.

Funding

Veru Inc.

Disclosure

M. Markowski: Research grant/Funding (institution): Veru Inc. M.A. Eisenberger: Shareholder/Stockholder/Stock options, Officer/Board of Directors: Veru Inc. R. Tutrone: Research grant/Funding (institution): Veru Inc. C. Pieczonka: Research grant/Funding (institution): Veru Inc. R.H. Getzenberg: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Veru Inc. D. Rodriguez: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Veru Inc. K.G. Barnette: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Veru Inc. M.S. Steiner: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Veru Inc. D.R. Saltzstein: Research grant/Funding (institution): Veru Inc. All other authors have declared no conflicts of interest.