VERU-111 has been shown to have high oral bioavailability, no expected allergic reactions, less possibility for drug resistance, as it does not interact with multiple drug resistance proteins, preventing it from being pumped out of the cancer cell. It also has the potential for the minimal drug to drug interactions; and high activity against many tumor types, including prostate cancer, which is resistant to drugs like abiraterone and enzalutamide, and taxanes. It also has beneficial activity in other cancers, including breast, ovarian, cervical, lung, melanoma, and pancreatic cancer.
Importantly, in preclinical and current clinical studies, VERU-111 appears to have no evidence of neurotoxicity and neutropenia, in contrast to taxanes and vinca alkaloids chemotherapy agents, which harbor these side effects quite commonly.
In this presentation, at the European Society of Medical Oncology – 2020 Virtual Congress (ESMO), Dr. Mark Markowski presented the VERU-111 phase 1b clinical trial, which took place in 7 United States (US) sites with a total of 39 enrolled patients in all sites. This was a dose-escalation phase 1b trial in men with metastatic castration-resistant prostate cancer (mCRPC) following at least one prior androgen receptor-targeted therapy. Patients could have one line of the previous taxane-based chemotherapy.
A two-part dosing schedule was used, with a standard 3*3 dose-escalation strategy. The demographics of patients are shown in table 1, and adverse effects are shown in table 2. The most common adverse events were diarrhea, fatigue, and nausea. Almost all adverse events were grades 1 and 2.
10 Men had reached at least four 21-day cycles of continuous dosing. Six of these men had prostate-specific antigen (PSA) decrease, two of them had a decrease of more than 50%, and the median duration of the treatment without radiographic progression was more than 11 months (range 6-17 months). Currently, 5/10 of the men are still on study.
Table 1 – study demographics:
Table 2- Treatment-related adverse events observed:
There is currently an ongoing phase 2 single-arm open-label study with anticipated complete accrual at the end of 2020. A total of 40 patients are planned with key eligibility criteria, including no prior taxane chemotherapy for mCRPC and prior treatment with at least one AR targeted therapy. The primary endpoint is radiographic progression-free survival and monitoring of safety.
In conclusion, VERU-111 appears to be well-tolerated in this phase 1b portion of the study. Evidence of anti-tumor activity was observed, including PSA reductions, objective tumor responses, and durable responses. The phase 2 portion of the study is currently ongoing.
Presented by: Mark Markowski, MD, Medical Oncology specialist, Sibley Memorial Hospital and The Johns Hopkins Hospital, Baltimore, Maryland
Written by: Hanan Goldberg, MD, MSc., Assistant Professor of Urology, SUNY Upstate Medical University, Syracuse, NY, USA @GoldbergHanan at the European Society for Medical Oncology Virtual Congress, ESMO Virtual Congress 2020 #ESMO20, 18 Sept - 21 Sept 2020
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