Date: 2017-12-21
Type of
information: update on patient enrollment
phase: 1b-2
Announcement: update on patient enrollment
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)
Action
mechanism:
- kinase 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.
Disease: acute myeloid leukemia (AML)
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
- The purpose of the phase 1b/2 study is to determine whether PCM-075 given orally daily for 5 consecutive days every 28 days is safe and tolerable in adult patients who have relapsed/refractory acute myeloid leukemia, or are ineligible for intensive induction therapy, and to determine the maximum tolerated dose or recommended phase 2 dose of PCM-075 in combination with decitabine or and PCM-075 in combination with low-dose cytarabine. In the phase 2 portion of the study, one regimen (either PCM-075 in combination with decitabine or PCM-075 in combination with low-dose cytarabine) will be studied to provide further data on the safety profile of the combination and to preliminarily assess the activity of the chosen combination in patients with untreated AML who are not candidates for aggressive induction therapy, or who have received one prior treatment for their AML.
- The Phase 1b/2 clinical trial in AML is being led by Hematologist Jorge Eduardo Cortes, M.D., Deputy Department Chair, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. (NCT03303339)
Latest
news:
- • On December 21, 2017, Trovagene announced the activation of the second clinical trial site for its Phase 1b/2 multicenter trial of PCM-075 in patients with AML, with Virginia Piper Cancer Institute and Principal Investigator, Dr. Michaela Tsai.
The primary objectives of this Phase 1b/2 trial in AML are to evaluate the safety of PCM-075 in combination with either low-dose cytarabine or decitabine in subjects and to identify the maximum tolerated dose (MTD) in Phase 1b to administer to further evaluate the safety and preliminary efficacy in Phase 2.
- • On November 13, 2017, Trovagene announced the activation of its clinical trial site for its Phase 1b/2 multicenter trial of PCM-075 in patients with acute myeloid leukemia, with Virginia Cancer Specialists and Principal Investigator, Dr. Alexander Spira. This trial will enroll subjects in the Phase 1b who have relapsed or have resistant disease to no more than three prior regimens.
Is
general: Yes
