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.
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.
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.
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
Legal entity responsible for the study
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.