Date: 2017-10-18
Type of
information: Results
phase: preclinical
Announcement: results
Company: Trovagene (USA - CA)
Product: PCM-075 (1-(2-hydroxyethyl)-8-{[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy) phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide fumarate salt) and Zytiga® (abiraterone acetate)
Action
mechanism:
- kinase inhibitor/androgen synthesis inhibitor. 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. Studies have shown that inhibition of polo-like-kinases can lead to tumor cell death, including a Phase 2 study in acute myeloid leukemia (AML) where response rates up to 31% were observed when used in conjunction with a standard therapy for AML (low-dose cytarabine-LDAC) versus treatment with LDAC alone with a 13.3% response rate. 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. Trovagene believes that targeting only PLK1 with reversible on-target activity and an improved dose/scheduling protocol can significantly improve on the long-term outcome observed in previous studies with a PLK inhibitor in AML. PCM-075 has demonstrated synergy in preclinical studies with over 10 chemotherapeutic and target agents used in hematologic and solid tumor cancers, including FLT3 and HDAC inhibitors, taxanes, and cytotoxins. Trovagene believes the combination of its targeted PLK-1 inhibitor, PCM-075, with other compounds has the potential for improved clinical efficacy in acute myeloid leukemia, castration-resistant prostate cancer, non-Hodgkin lymphoma, triple negative breast cancer and adrenocortical carcinoma.
- Zytiga® (abiraterone acetate), a CYP17-inhibitor, inhibits the key enzyme which modulates the production of androgens, hormones which stimulate prostate cancer cells to grow, from all sources in the body. This helps lower the level of androgens available to the prostate cancer cells, which is the goal of treatment in prostate cancer. This drug is indicated for the treatment of mCRPC in combination with prednisone.
Disease: metastatic prostate cancer
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
Latest
news:
- • On October 18, 2017, Trovagene announced positive data from preclinical research demonstrating synergy of PCM-075, its oral, highly-selective Polo-like Kinase 1 (PLK1) Inhibitor, in combination with abiraterone (Zytiga® - Johnson & Johnson). This research was performed in collaboration with a major cancer research institution. "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," said Dr. Mark Erlander, Chief Scientific Officer of Trovagene. "This unique combination appears to enhance the PCM-075 mechanism of action of arresting cells during mitosis with subsequent tumor cell death."
Is
general: Yes
