Date: 2017-12-07
Type of
information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the 40th San Antonio Breast Cancer Symposium (SABCS)
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: triple-negative breast cancer (TNBC)
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
Latest
news:
- • On December 7, 2017, preclinical data demonstrating the sensitivity of triple negative breast cancer (TNBC) cell lines to Trovagene's PCM-075, a highly selective Polo-like kinase 1 (PLK1) Inhibitor, have been featured as a Poster Presentation at the 40th San Antonio Breast Cancer Symposium (SABCS) .Trovagene's poster entitled, Sensitivity of Triple Negative Breast Cancer Cell Lines to PCM-075, a Highly Selective Polo-like Kinase 1 Inhibitor, presents the preclinical analysis of 40 cancer cell lines and demonstrates that triple negative breast cancer (TNBC) cell lines are 20-fold more sensitive to PCM-075 than estrogen receptor positive (ER+) breast cancer cells lines.
Polo-like Kinase 1 (PLK1) is known to be over-expressed in many hematologic and solid tumor cancers, including breast cancer. PLK1 inhibition by PCM-075 induces cell-cycle arrest and apoptosis, or tumor cell death in numerous tumor cell lines, including TNBC cell lines. Additionally, a subset of TNBC cell lines harbor the androgen receptor (AR) and androgen can promote tumor growth. The presentation data indicates that PCM-075 in combination with anti-androgen, abiraterone acetate (Zytiga® - Johnson & Johnson), are synergistic in inducing cell death within an AR+ TNBC cell line.
Is
general: Yes
