Trovagene will soon begin patient recruitment for its Phase 2 clinical trial evaluating PCM-075 in combination with Zytiga (abiraterone acetate) and prednisone for the treatment of metastatic, castration-resistant prostate cancer (mCRPC).
The study (NCT03414034) will enroll patients at Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute, and Massachusetts General Hospital, the three centers where the trial will be conducted.
PCM-075 is a selective polo-like kinase 1 (PLK1) inhibitor. PLK1 is a protein whose levels are particularly high in cancer cells, which often is associated with poor outcomes. PCM-075 could help trigger the death of cancer cells by inhibiting PLK1.
In mCRPC, either levels of the biomarker prostate specific antigen (PSA) continue to rise or new symptoms appear after patients are treated with hormone therapies. Metastatic cancers are those that also spread to other parts of the body.
Preclinical studies have shown that PCM-075 increases the punch of Zytiga, one of the world’s leading therapies for mCRPC. Zytiga works by decreasing the levels of male hormones associated with cancer.
“The synergy observed when we combined PCM-075 with abiraterone appears to work through a novel mechanism that may modulate a signaling pathway previously unknown to be associated with this combination,” Mark Erlander, Trovagene’s chief scientific officer, said in the press release with the preclinical findings. “This unique combination appears to enhance the PCM-075 mechanism of action of arresting cells during mitosis, with subsequent tumor cell death.”
Mitosis is the process by which cells divide, meaning that stopping cells during mitosis prevents this division and further development of cancer.
In this new Phase 2 study, PCM-075 will be studied in combination with a standard dose of Zytiga and prednisone, all through oral administration. Researchers will look into the safety and efficacy of the combination treatment in up to 45 patients with mCRPC.
The primary efficacy endpoint is the proportion of patients who achieve disease control after 12 weeks of treatment. This is defined by lack of PSA progression in patients showing signs of early progressive disease while receiving Zytiga and prednisone.
Additional endpoints include measures of response and progression, as well as safety.
“Prostate cancer will kill an estimated 29,430 men in the United States this year. It is clear that resistance to standard therapies continues to be an urgent problem for our patients,” lead researcher David Einstein, MD, said in a press release.
More information about eligibility criteria for the trial can be found here.