Veru said it initiated the Phase 2 portion of a clinical trial testing the safety and effectiveness of its investigational therapy, VERU-111, in men with metastatic castration-resistant prostate cancer (mCRPC) who failed to respond to a novel androgen receptor inhibitor.
The announcement comes after the Phase 1b part of the trial, a dose-escalation study in 39 patients, showed positive safety and activity results and identified the optimal dose of VERU-111 for this prostate cancer population. The Phase 2 part, which has dosed its first patient, will continue to study the safety and efficacy of this dose.
“Having seen both preliminary evidence of prostate cancer antitumor activity and an acceptable safety profile in the Phase 1b portion of the clinical trial, we are very excited to now be able to advance VERU-111 into the Phase 2 portion of the clinical trial,” Mitchell Steiner, MD, chairman, president and chief executive officer of Veru, said in a press release.
“The first patient in the Phase 2 study has been dosed, representing a key milestone in the clinical development of VERU-111,” Steiner said. “We expect results from this Phase 2 study by the end of the current calendar year.”
“Moreover, since the study is open label, we anticipate being able to update investors periodically as to progress being made in the trial,” he said.
VERU-111 is a first-in-class oral agent that targets tubulin, a component of microtubules, disrupting these structures. Microtubules are dynamic structures that form part of the cell’s cytoskeleton, providing shape to cells and helping them move and divide.
Some chemotherapies, called taxanes —including Jevtana (cabazitaxel) and docetaxel — are already approved in the U.S. to treat metastatic prostate cancer by targeting microtubules. However, these are given intravenously, and are associated with resistance and safety concerns.
VERU-111 has shown significant anti-tumor activity against prostate cancers that no longer respond to androgen deprivation therapies or second-generation androgen receptor inhibitors such as Zytiga (abiraterone acetate) or Xtandi (enzalutamide) in preclinical studies.
The investigational therapy showed efficacy against cancers that produced proteins involved in treatment resistance, according to Veru’s website.
The ongoing Phase 1/2 trial was designed to study VERU-111 in men with mCRPC who failed prior treatment with therapies such as Zytiga or Xtandi. Phase 1 results showed that treatment was well tolerated by patients, with no reports of toxicity to the nervous system, allergic reactions, or fever caused by low white blood cell levels — all common side effects of intravenous taxane chemotherapy.
Four of the men enrolled in the Phase 1b trial showed no signs of disease progression at intervals ranging from 7.6 months to 11.75 months. Two showed no progression at 10.4 months, and all experienced reductions in their prostate specific antigen (PSA) levels — a biomarker of prostate cancer.
This is noteworthy, as control men with similar cancers see their cancer progress after an average of 3.7 months. Six other men in the trial progressed at 4.2 months.
The Phase 2 portion of the trial aims to evaluate the effectiveness and safety of VERU-111 in an additional 39 mCRPC patients who have also become resistant to a second-generation androgen blocking agent. While the Phase 1 part included patients who could have received one prior taxane chemotherapy, patients in this part must be naive to prior chemotherapy.
Patients will receive a daily dose of 63 mg of VERU-111, but dose increases to up to 72 mg will be allowed.
The main goals of this part are to determine the time patients live without disease worsening, assessed by radiographic imaging, and reductions in PSA levels reduction.
“VERU-111 is initially targeting men who have metastatic castration resistant prostate cancer (mCRPC) and who have also become resistant to novel androgen blocking agents, such as abiraterone or enzalutamide, but prior to proceeding to IV chemotherapy — also referred to as the prechemotherapy stage,” Steiner said.
“This prechemotherapy stage in men is currently one of the fastest growing unmet medical needs in advanced prostate cancer,” he said. “We are developing VERU-111 to be the next go to therapy in men with advanced prostate cancer who fail a novel androgen blocking agent.”