FDA Offers Feedback on Phase 3 Trial Design of VERU-111 in Prostate Cancer

The Food and Drug Administration (FDA) issued regulatory clarity on the pivotal phase 3 trial design for VERU-111 being evaluated in metastatic castration and novel androgen-blocking agent resistant prostate cancer.

In particular, the agency noted the trial design was acceptable. The open label, randomized, active control study using an alternative novel androgen blocking agent as the active control was found to be reasonable. Moreover, the FDA said that the primary end point will be radiographic progression-free survival in the pre-chemotherapy patient population.

“Input from the FDA was very positive and constructive regarding the VERU-111 pivotal phase 3 trial design,” Dr. Mitchell Steiner, chairman, president and CEO of Veru, said in a press release. “…By allowing radiographic progression-free survival as an end point, the sample size of the phase 3 study could be much smaller—potentially between 200 and 300 men.”

Veru intends to submit a final phase 3 protocol to the FDA by the end of 2020, with the goal of starting the study by the first quarter of 2021, according to the release.

The company also noted that clinical results from its phase 1b/2 study of VERU-111 for the treatment of men with metastatic castration resistant prostate cancer who failed an androgen blocking agent will be presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, to be held Sept. 19 to 21.

“We are looking forward to sharing the clinical results evaluating VERU-111 in a phase 1b/2 trial in men with metastatic castration and androgen receptor targeting agent resistant prostate cancer,” Steiner said in a press release.“The presentation will focus on the clinical data from the phase 1b clinical study. The ongoing phase 2 clinical study portion has almost completed enrollment.”

In the phase 1b study, VERU-111 appeared to be well tolerated with no reports of neurotoxicity, allergic reactions and febrile neutropenia. Among 20 men in the study, four men are still ongoing in the trial with no progression at 11.75, 10.4, 10.4 and 7.6 months, even without an optimal dose or dose schedule to be determined yet.

“There is also evidence that these anticancer effects appear to have a dose response, meaning higher doses at 3-week cycles have more activity,” the company said in a release.

The open label, single arm, phase 2 clinical trial is designed to evaluate the efficacy and safety of VERU-111 in 39 patients who have become resistant to a secondary novel androgen blocking agent. The key efficacy end points are radiographic imaging of progression-free survival and prostate-specific antigen reductions.

VERU-111 is an oral, first-in-class, novel alpha and beta tubulin targeting drug candidate being evaluated for the treatment of metastatic castration and novel androgen-blocking agent resistant prostate cancer.

“The treatment of men with metastatic castration resistant prostate cancer usually involves the use of one or more novel androgen receptor targeting drugs followed by standard taxane based intravenous chemotherapy,” Dr. Mario Eisenberger, the R. Dale Hughes Professor of Oncology and Urology at the Johns Hopkins Hospital and a director at Veru, said in the release.

“The promising preliminary evidence of safety and efficacy of VERU-111 provides an excellent opportunity for the treatment of metastatic castration resistant prostate cancer clinical paradigm of unmet need.”