Greater selectivity for PLK1, potency, oral bioavailability and short half-life underscore PCM-075’s potential as safe and effective treatment for solid tumor and hematological malignancies

SAN DIEGO, CA, USA I July 25, 2017 I Trovagene, Inc. (NASDAQ:  TROV), a precision medicine biotechnology company, today announced the publication of clinical results from a Phase 1 dose escalation study of PCM-075 (formerly NMS-1286937) in patients with advanced or metastatic solid tumors in the peer-reviewed journal Investigational New Drugs.  PCM-075 is an investigational, orally available, highly-selective PLK1 inhibitor.

The publication, entitled “Phase 1 Dose-Escalation Study of NMS-1286937, an Orally Available Polo-Like Kinase 1 Inhibitor, in Patients with Advanced or Metastatic Solid Tumors,” presents results from a Phase 1, open-label, dose escalation trial performed by Nerviano Medical Sciences in patients with solid tumors, including colorectal (n=4), pancreatic (n=4), lung (n=2), sarcomas (n=2) and single patients representing hepatocellular, ampullary, prostate, ovarian and skin cancers.

PCM-075 was administered orally, once daily for five consecutive days, every three weeks, to evaluate drug metabolism, first cycle dose-limiting toxicities (DLTs) and related maximum tolerated dose (MTD). The study also evaluated PCM-075’s pharmacokinetic profile in plasma, its anti-tumor activity, and its ability to modulate intracellular targets in biopsied tissue. The average age of patients enrolled was 63 years and nearly eighty percent had received between 3 to 7 previous anti-cancer therapies prior to study enrollment. 

This first-in-human phase 1 study established safety of PCM-075 and successfully identified a recommended Phase 2 dose (RP2D) of 24 mg/m2/day for treating solid tumors. Of the 21 patients enrolled, 19 received a total of 44 cycles of treatment with a median number of cycles per patient of 2 (range 1-6). Sixteen of the 19 patients (84.2%) enrolled in the study were evaluable for efficacy, with stable disease observed in 5 of the 16 (31.2%) patients, including patients with colorectal (2), pancreatic (1), head and neck (1), and basal cell carcinoma (1).

The study identified thrombocytopenia and neutropenia as the primary on-target toxicities, which is consistent with the expected mechanism of action of PCM-075 and results from preclinical studies. These hematologic toxicities were reversible, with recovery occurring within 3 weeks. One patient experienced grade 3 constipation adverse event, which authors conclude likely was due to concomitant treatment with opiates. No other clinically relevant safety findings emerged. 

“The data from this first-in-human trial demonstrated that PCM-075 is generally safe and well-tolerated in patients with advanced cancers,” said Dr. Glen Weiss, principal investigator and first author. “Data from preclinical work, coupled with the results of the Phase 1 trial, suggest that PCM-075 could become a new therapeutic option for the treatment of solid tumors and hematological malignancies, including acute myeloid leukemia.”

“We are pleased to see the publication of the Phase 1 data in Investigational New Drugs,” said Bill Welch, Chief Executive Officer of Trovagene. “This peer-reviewed publication shows the potential for PCM-075, including patients with hematological malignancies as a possible target population for PLK1 inhibition. The safety data are supportive of our planned Phase 1b/2 clinical trial in patients with acute myeloid leukemia and we look forward to reporting our clinical development progress with PCM-075.”

About 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 several different hematologic malignancies, as well as solid tumors such as 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.

About Trovagene, Inc.

Trovagene is a precision medicine biotechnology company developing oncology therapeutics for improved cancer care by leveraging its proprietary Precision Cancer Monitoring® (PCM) technology in tumor genomics.  Trovagene has broad intellectual property and proprietary technology to measure circulating tumor DNA (ctDNA) in urine and blood to identify and quantify clinically actionable markers for predicting response to cancer therapies.  Trovagene offers its PCM technology at its CLIA/CAP – accredited laboratory and plans to continue to vertically integrate its PCM technology with precision cancer therapeutics.  For more information, please visit https://www.trovagene.com.

SOURCE: Trovagene