VERU-111 demonstrated antitumor activity and durable PSA declines in men with metastatic castration-resistant prostate cancer who are resistant to at least 1 novel androgen-blocking agent.
Mario Eisenberger, MD
The first-in-class, oral, selective antitubulin agent VERU-111 demonstrated antitumor activity and durable PSA declines in men with metastatic castration-resistant prostate cancer (mCRPC) who are resistant to at least 1 novel androgen-blocking agent, according to phase 1b/2 clinical trial findings announced by Veru Inc., the company developing the treatment.
Veru reported results from the phase 1b portion of the study. Among 8 patients, the median duration of tumor response without cancer progression was 10 months (range, 6-14). Seven of the 8 patients are still receiving VERU-111 with no evidence of tumor progression.
“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. As predicted, most responses occurred around the recommended phase 2 dose and schedule,” Mario Eisenberger, MD, R. Dale Hughes Professor of Oncology And Urology at the Johns Hopkins Hospital and a director at Veru Inc., stated in a press release.
“All patients at the time of enrollment had evidence of disease progression with at least 1 novel androgen receptor targeting drug (abiraterone acetate [Zytiga] and enzalutamide [Xtandi]). The initial clinical experience with VERU-111 appears favorable in the context of other FDA approved cytotoxic drugs (docetaxel and cabazitaxel [Jevtana]) in metastatic castration-resistant prostate cancer. As for safety, the lack of neurotoxicity and the lack of significant myelosuppression observed thus far, coupled with the evidence that chronic long-term administration is feasible, strongly support the potential benefits of VERU-111 over IV cytotoxic taxanes in this setting,” added Eisenberger.
Overall, 39 patients from 7 US clinical locations were enrolled in the phase 1b part of the study. Oral dosing of VERU-111 was escalated from 4.5 mg to 81 mg, with patients receiving daily treatment for 7 days followed by no drug for 14 days of each 21-day cycle. The maximum-tolerated dose was determined to be 72 mg. At that dose level, 3 of 11 men had reversible grade 3 diarrhea. At doses under 72 mg daily, no grade 3 diarrhea was reported.
The investigators considered VERU-111 to be safe and well tolerated at doses of ≤63 mg daily. At these doses, the most common adverse events were mild-to-moderate nausea, vomiting, diarrhea, and fatigue. Also, there were no cases of neurotoxicity or neutropenia reported at these dose levels.
The investigators assessed efficacy by serum PSA and standard local imaging with bone and CT scans. Efficacy findings were determined in the 8 men treated with 4 or more 21-day cycles at any dose. Six (75%) of the 8 men had a decrease in their serum PSA level, with 4 men achieving a ≥30% decline, and 50% reaching a ≥50% decline. Two patients had objective tumor responses and 5 patients had stable disease. The median duration of response and median time to cancer progression have not yet been reached. Three additional patients are on study but have not yet finished four 21-day cycles.
“I am very pleased to update you with the exciting results of our VERU-111 phase 1b portion of the phase 1b/2 clinical trial,” Mitchell Steiner, MD, chairman, president and chief executive officer of Veru, stated in the press release. “VERU-111 has promising antitumor activity with a good safety profile. The clinical development goal is to position VERU-111, which has a unique drug mechanism of action that does not target the androgen receptor, as the next “go to drug” in men who have metastatic castration-resistant prostate cancer and who have evidence of prostate cancer progression while being treated with an androgen blocking agent like abiraterone or enzalutamide, but prior to using “off label” IV chemotherapy. These clinical results firmly position Veru as an oncology focused biopharmaceutical company. We will meet with FDA next quarter to gain agreement on the registration phase 3 design for this indication. We also plan to present an update of the phase 1b/2 clinical data at the next possible upcoming major scientific meeting.”
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. Published May 5, 2020. https://bit.ly/3dolLnn. Accessed May 5, 2020.