Veru has completed enrollment for the second portion of a Phase 1/2 study of VERU-111, its investigational therapy for men with metastatic castration-resistant prostate cancer (mCRPC) who failed to respond to treatment with a new androgen receptor inhibitor.

The open-label Phase 1/2 trial (NCT03752099) will evaluate the compound’s safety and efficacy in 40 men with mCRPC at 13 clinical sites across the U.S., including multiple centers in Texas and Maryland.

All study participants have mCRPC that has grown resistant to at least one form of hormone therapy, such as Zytiga (abiraterone acetate) or Xtandi (enzalutamide), but who have not yet begun intravenous (into-the-vein) chemotherapy. Both Zytiga and Xtandi target and block the activity of the androgen receptor, preventing it from interacting with male hormones that promote prostate cancer cells’ survival.

Men enrolled in the trial will receive 63 mg of VERU-111 per day, which was established as the optimal dose in the first portion of the study. The first patient participating in the second portion of the trial was dosed in March.

The main goal of this portion of the study is to determine the time patients live without showing signs of disease progression, which will be evaluated by radiographic imaging.

Additional goals include determining the proportion of patients who respond to treatment, and the percentage of those who see their prostate-specific antigen (PSA; a marker of prostate cancer) levels drop by at least 50% from the study’s start. The incidence and severity of adverse events, or undesirable side effects, also will be assessed.

“We are excited to have fully enrolled the Phase 2 portion of the Phase 1b/2 clinical trial evaluating the recommended 63 mg oral daily continuous dosing of VERU-111 for metastatic castration and androgen receptor targeting agent resistant prostate cancer,” Mitchell Steiner, MD, president and CEO of Veru, said in a press release.

VERU-111 is an oral compound that targets tubulin, a component of cell microtubules — dynamic structures that give cells shape, while helping them move and divide. By disrupting the structure and function of microtubules in cancer cells, VERU-111 is expected to interfere with their ability to proliferate, staving off their growth.

Additionally, compared with certain chemotherapy agents that also target microtubules, VERU-111 potentially may be safer and less likely to be associated with treatment resistance.

Data from the first phase of this trial, recently presented by the company at the European Society for Medical Oncology (ESMO) Congress 2020, showed VERU-111 was well-tolerated. There were no cases of neurotoxicity, allergic reactions, nor neutropenia (low white blood cell counts).

VERU-111 also showed promising anti-tumor activity, with six out of the 10 men who completed at least four cycles of treatment seeing their PSA levels drop; additionally, two saw their tumors shrink.

Those who received the medication at a dose of 63 mg in the first portion of the study lived a median of 9.8 months without showing signs of disease worsening. This is much longer than the median time (2.6 months) men with mCRPC who failed to respond to both Zytiga and Xtandi lived without disease worsening.

Based on these promising findings, the company is now planning to move ahead and submit the final protocol of a Phase 3 pivotal trial of VERU-111 to the U.S. Food and Drug Administration (FDA) before the end of the year.

This new Phase 3 trial, which will assess the safety and efficacy of VERU-111 in men with mCRPC who failed to respond to at least one androgen receptor targeting agent, is expected to launch in early 2021. The company also is planning to meet with the European Medicines Agency (EMA) next year to pursue the therapy’s development in the EU.

VERU-111 also is being tested in a separate Phase 2 trial (NCT04388826) as a possible treatment for those with COVID-19. That trial seeks to demonstrate the efficacy of VERU-111 in people with COVID-19 by assessing the therapy’s effect on the proportion of patients who are alive without respiratory failure at 22 days after treatment.