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


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.

Mitchell Steiner, MD

Mitchell Steiner, MD

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.
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