On June 21, 2018 Trovagene, Inc. (NASDAQ: TROV), a clinical-stage oncology therapeutics company, developing targeted therapeutics for the treatment of hematologic and solid tumor cancers, reported they have received Institutional Review Board (IRB) approval from Dana-Farber/Harvard Cancer Center and its Phase 2 clinical trial of PCM-075 in combination with Zytiga (abiraterone acetate) and prednisone in metastatic Castration-Resistant Prostate Cancer (mCRPC) is officially activated and recruiting patients (Press release, Trovagene, JUN 21, 2018, View Source [SID1234527420]). The trial is being conducted by Beth Israel Deaconess Medical Center (BIDMC), Dana-Farber Cancer Institute (Dana-Farber), and Massachusetts General Hospital Cancer Center (MGH). David Einstein, MD, Genitourinary Oncology Program at BIDMC, is the principal investigator for the trial.
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In this multi-center, open-label, Phase 2 trial, PCM-075 in combination with the standard dose of Zytiga (abiraterone acetate) and prednisone, all administered orally, will be evaluated for safety and efficacy. The Phase 2 clinical trial will enroll up to 45 patients, with mCRPC, showing signs of disease progression demonstrated by two rising PSA values separated by at least one week, while on abiraterone acetate and prednisone therapy. The primary efficacy endpoint is the proportion of patients achieving disease control after 12 weeks of study treatment, as defined by lack of prostate specific antigen (PSA) progression in patients who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving abiraterone acetate and prednisone.
"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. Pre-clinical work has identified polo-like kinase 1 as a drug target meriting study in combination with abiraterone," said Dr. Einstein.
"We are excited to be working with the Dana-Farber/Harvard Cancer Center and look forward to evaluating the impact of PCM-075 in combination with abiraterone acetate in patients with mCRPC," said Bill Welch, Chief Executive Officer of Trovagene.
About Castration-Resistant Prostate Cancer (CRPC)
Castration-Resistant Prostate Cancer (CRPC) is defined by disease progression despite androgen-deprivation therapy (ADT) and may present as one or any combination of a continuous rise in serum levels of prostate-specific antigen (PSA), progression of pre-existing disease, or appearance of new metastases. Prognosis is associated with several factors, including performance status, presence of bone pain, extent of disease on bone scan, and serum levels of alkaline phosphatase. Bone metastases occur in 90% of men with CPRC and can produce significant morbidity, including pain, pathologic fractures, spinal cord compression, and bone marrow failure. Paraneoplastic effects are also common, including anemia, weight loss, fatigue, hypercoagulability, and increased susceptibility to infection. Institution of treatment and the choice of systemic or local therapy depend on a number of factors.
About PCM-075
PCM-075 is a highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple hematologic and solid tumor cancers. PCM-075 only targets PLK1 isoform (not PLK2 or PLK3), is oral, has a 24-hour drug half-life with reversible on-target hematologic toxicities. A Phase 1 open-label, dose escalation safety study of PCM-075 has been completed in patients with advanced metastatic solid tumor cancers and published in 2017 in Investigational New Drugs. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) in this trial was 24 mg/m2.
PCM-075 has demonstrated synergy in preclinical studies with over 10 chemotherapeutic and target agents used in hematologic and solid tumor cancers, including abiraterone acetate (Zytiga), FLT3 and HDAC inhibitors, taxanes, and cytotoxins. Trovagene believes the combination of its targeted PLK1 inhibitor, PCM-075, with other compounds has the potential for improved clinical efficacy in Acute Myeloid Leukemia (AML), metastatic Castration-Resistant Prostate Cancer (mCRPC), Non-Hodgkin Lymphoma (NHL), Triple Negative Breast Cancer (TNBC), as well as other hematologic and solid tumor cancers.
Trovagene has a Phase 2 trial of PCM-075 in combination with abiraterone acetate (Zytiga) in metastatic Castration-Resistant Prostate Cancer currently recruiting and enrolling patients that was accepted by the National Library of Medicine (NLM) and is now publicly viewable on www.clinicaltrials.gov. The NCT number assigned by clinicaltrials.gov for this study is NCT03414034.