Trovagene, a precision medicine biotechnology company, announced compelling results of preclinical research of PCM-075 with a Histone deacetylase (HDAC) inhibitor in Non-Hodgkin Lymphoma (NHL) cell lines. This synergy assessment study was conducted by Dr. Steven Grant, Associate Director for Translational Research and co-Leader, Developmental Therapeutics Program, Massey Cancer Center.
PCM-075, Trovagene's investigational Polo-like kinase 1 (PLK1) inhibitor, showed significant synergy in combination with a HDAC inhibitor of up to 80% in aggressive double-hit B-cell lymphoma (DLBCL) and mantle-cell lymphoma cell lines. DLBCL and mantle cell lymphomas within NHL represent challenging malignancies without a standard-of-care treatment and confer a poor prognosis for patients.
Additionally, PCM-075 synergy has been evaluated in combination with more than ten different chemotherapeutics, including cisplatin, cytarabine, doxorubicin, gemcitabine and paclitaxel, and targeted therapies, such as HDAC inhibitors, FLT3 inhibitors, and bortezomib. These therapeutics are used clinically for treatment of many solid and hematologic cancers, including Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Non-Hodgkin Lymphoma (NHL), Multiple Myeloma, Adrenocortical Carcinoma (ACC), Triple-Negative Breast Cancer (TNBC), Small-Cell Lung Cancer (SCLC), and Ovarian Cancer.
"We are excited to see the synergistic benefits with PCM-075 in combination with a HDAC inhibitor in the most difficult cell lines in NHL," said Bill Welch, CEO of Trovagene. "This data complements our recent announcement of an in-vivo study demonstrating synergy of PCM-075 with a leading investigational FLT3 inhibitor, as well as PCM-075 synergy with many chemotherapeutics. We have an active Investigational New Drug (IND) in place with the FDA for each of solid tumors and hematologic malignancies, which could facilitate the development of PCM-075 across a number of cancer types."
The consistent and significant synergistic effects observed in preclinical research on tumor cell death indicates that PCM-075 could be effective in combination therapies to address a broad range of tumor types, as well as the emergence of drug-resistant tumors.
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 malignancies, as well as solid tumors such as adrenocortical, breast, prostate, ovarian, lung, gastric and colon cancers. PCM-075 is orally bioavailable and has been explored in an initial Phase 1, open-label, dose-escalation safety study in patients with advanced metastatic solid tumor cancers. Trovagene plans to initiate clinical trials of PCM-075 in AML, since it has significant advantages over prior PLK1 inhibitors evaluated in this indication, including a higher selectivity, greater potency, oral bioavailability and shorter half-life.