Trovagene, a precision medicine biotechnology company, announced summary data from a phase I safety study conducted by Nerviano Medical Sciences with PCM-075, a polo-like kinase 1 (PLK1) inhibitor. This data is supportive of a planned phase I/II clinical trial in patients with acute myeloid leukemia (AML) and is now being submitted for peer review publication by study investigators.
The phase I safety study was an open-label, dose-escalation trial in patients with advanced or metastatic solid tumors. PCM-075 was administered orally, once daily for five consecutive days, every day for three weeks, to evaluate drug metabolism and 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 phase I study enrolled 21 patients with confirmed metastatic disease and a mean age of 62.7 years. These patients received study medication at doses up to 48mg/m2/day. The most common cancer types for enrolled patients included colon, pancreatic, lung and head and neck cancer.
Thrombocytopenia and neutropenia were identified as the primary DLTs, which are consistent with the expected mechanism of action and results from preclinical studies. These hematologic toxicities were reversible. One patient experienced grade three constipation, which may have been due to concomitant treatment with opiates. No other clinically relevant safety findings emerged.
"Hematologic side effects are expected with PLK inhibitors, which induce mitotic cell cycle arrest preferentially in rapidly proliferating blood cells, leading to cell death. This suggests anti-tumor activity in hematologic malignancies and supports our plans to develop PCM-075 for the treatment of AML," said Dr. Mark Erlander, chief scientific officer of Trovagene. "We believe the phase 1 data indicates broad applications for PCM-075 in hematologic malignancies and solid tumors and we plan to continue to assess, and explore, additional precision cancer therapeutic opportunities going forward."
The complete phase I data, study details and conclusions are part of the manuscript that will be submitted by study investigators for peer review publication.