Trovagene Announces Activation of First Clinical Trial Site in AML Trial

Trovagene announced the activation of its clinical trial site for its Phase 1b/2 multicenter trial of PCM-075 in patients with AML, 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. The Phase 1b is a dose escalation study to determine a recommend phase 2 dose.  The Phase 2 continuation study will provide preliminary evaluation of anti-leukemic activity and will enroll newly diagnosed subjects, judged to be ineligible for, or who have refused, standard intensive induction therapy, as well as subjects who have relapsed after treatment with no more than one prior regimen.

"PCM-075 is the first highly PLK1-selective competitive inhibitor administered orally to enter clinical trials with potential activity in both hematologic and solid tumor cancers," said Bill Welch, Chief Executive Officer of Trovagene. "We are excited to have Virginia Cancer Specialists as our first clinical trial site ready to screen and enroll subjects in our PCM-075 AML trial."

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.

"As the only dedicated Phase 1 oncology research facility in Northern Virginia, we are pleased to be a part of this important clinical trial and to investigate this promising alternative therapy in AML patients," said Dr. Alexander Spira, Co-Director Clinical Research, Director Phase 1 Program, Virginia Cancer Specialists. "Through this Phase 1b/2 clinical trial, we look forward to gaining insight into the safety, tolerability and initial efficacy of 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. 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. 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 Investigational New Drugs. Trovagene is initiating a Phase 1b/2 clinical trial with PCM-075 in AML 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 NCT03303339. PCM-075 has been granted Orphan Drug Designation by the FDA for the treatment of patients with AML.

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 (AML), Castration-Resistant Prostate Cancer (CRPC), Non-Hodgkin Lymphoma (NHL), Triple Negative Breast Cancer (TNBC) and Adrenocortical Carcinoma (ACC).

Acute myeloid leukemia (AML) is a hematologic malignancy in which myeloid lineage cells of the bone marrow cease to differentiate appropriately, resulting in a marked increase in the number of circulating immature blast cells. As a consequence, the counts of mature red blood cells, platelets, and normal white blood cells decline, causing fatigue, shortness of breath, bleeding, and increased susceptibility to infection. The Surveillance, Epidemiology and End Results (SEER) program estimates the annual incidence rate of AML in the United States US to be approximately 21,000 cases in 2017. Rates of new AML cases have been rising an average of 3.1% each year over the last 10 years. The median age of AML diagnosis is 68 years of age, and approximately 45% of new diagnoses are among patients age 70 years or older.