FDA Provides Regulatory Clarity on Phase 3 Trial Design for VERU-111 in mCRPC

Hayley Virgil
Hayley Virgil

Senior Editor, OncLive®
Hayley Virgil heads OncLive's feature article efforts and specializes in social issues and equality in oncology. Prior to joining the company in early 2020, she worked as an editor in numerous industries, including media, marketing, hospitality, and computer science, and freelanced in subjects such as history, culture, and the natural sciences.

The FDA has provided regulatory clarity on the design of the pivotal phase 3 trial examining the first-in-class oral, oral, selective antitubulin agent VERU-111 in the treatment of patients with metastatic castration-resistant prostate cancer.

The FDA has provided regulatory clarity on the design of the pivotal phase 3 trial examining the first-in-class oral, oral, selective antitubulin agent VERU-111 in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC), according to an announcement from Veru Inc, the developer of the drug.1

“Input from the FDA was very positive and constructive regarding the VERU-111 pivotal phase 3 trial design,” Mitchell Steiner, MD, the chairman, president, and CEO of Veru, stated in a press release. “We received clarity that the indication, metastatic castration and novel androgen blocking agent resistant prostate cancer, which is a prechemotherapy population, was acceptable, and that an open label, randomized, active control study using an alternative novel androgen-blocking agent as the active control is reasonable, and that the primary end point will be radiographic progression-free survival (rPFS).”

By allowing rPFS to serve as the primary end point, the sample size for the phase 3 trial could be much smaller, between 200 and 300 patients, according to Steiner.

The open-label, phase 3 trial will evaluate the safety and efficacy of VERU-111 compared with an androgen-blocking agent, either abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in patients with mCRPC who progressed on an androgen-blocking agent, according to the clinical development plan.2 Specifically, patients randomized to the investigational arm will receive oral VERU-111 at 63 mg daily dosing for 21-day treatment cycles.

Previous data from a phase 1b/2 clinical trial revealed that VERU-111 demonstrated notable antitumor activity and resulted in durable prostate-specific antigen (PSA) reductions in patients with mCRPC who were resistant to at least 1 novel androgen-blocking agent.3

Of 8 patients, the median duration of tumor response without cancer progression was 10 months, and 7 patients were still receiving the treatment without any evidence of disease progression at the time that the data were reported.

Among the 8 men who were treated with 4 or more 21-day cycles at any dose of VERU-111, 6 (75%) experienced a decrease in their serum PSA levels; 4 of these patients had a ≥30% reduction while the other half of the patients achieved a ≥50% decline. Two of the patients experienced objective tumor responses to the treatment and 5 achieved stable disease.

“All patients at the time of enrollment had evidence of disease progression with at least 1 novel androgen receptor–targeting drug. The initial clinical experience with VERU-111 appears favorable in the context of other FDA approved cytotoxic drugs (docetaxel and cabazitaxel [Jevtana] in mCRPC,” Mario Eisenberg, MD, of Johns Hopkins Hospital, had stated in a press release.

A total of 39 patients were enrolled on the phase 1b portion of the trial at 7 clinical locations across the United States. In the trial, investigators escalated the dose of the agent from 4.5 mg to 81 mg. Patients were given daily treatment for 7 days; this was followed with no drug for 2 weeks of each 21-day cycle. Investigators identified the maximum-tolerated dose to be 72 mg. At this dose, 3 of 11 patients reported grade 3 reversible diarrhea. No grade 3 events were reported in patients who received doses under the 72-mg daily dose.

With regard to safety, the agent was found to be well tolerated when administered at doses of ≤63 mg daily. At that dosage, the most common toxicities reported included mild-to-moderate nausea, vomiting, diarrhea, and fatigue. Notably, no patients experienced neurotoxicity or neutropenia at these dose levels.

Currently, 10 men are enrolled on the study with 7 receiving ≥4 continuous dosing for 21-day cycles and 3 receiving ≤4 continuous dosing for 21-day cycles, according to Veru, Inc.

“The preliminary evidence of antitumor activity and favorable safety profile of VERU-111 observed in the dose-escalation and expansion phase 1b study is quite encouraging,” Eisenberger added. “As predicted, most responses occurred around the recommended phase 2 dose and schedule.”

The biopharmaceutical company plans to submit the final phase 3 trial protocol to the FDA in Q4 2020, and they also plan to meet with the European Medicines Agency. The phase 3 trial is anticipated to launch in Q1 2021, according to Steiner.


  1. Veru receives positive input from FDA on phase 3 pivotal trial to evaluate VERU-111 in metastatic castration resistant prostate cancer. News release. Veru, Inc. July 23, 2020. Accessed July 29, 2020. https://bit.ly/3hNoKaY.
  2. VERU-111, an oral, next generation, first-in-class small molecule for the treatment of metastatic prostate and other cancers. Veru, Inc website. Accessed July 29, 2020. https://verupharma.com/pipeline/veru-111/.
  3. Veru reports positive clinical results from VERU-111 phase 1b/2 trial in men with metastatic castration-resistant prostate cancer, advancing to pivotal phase 3 clinical program. News release. Veru, Inc. Accessed July 29, 2020. https://bit.ly/3dolLnn.