US-based OncoMed Pharmaceuticals has initiated a multi-centre Phase Ib clinical trial involving its first-in-class Wnt-pathway-targeting decoy receptor OMP-54F28 (Fzd8-Fc) with sorafenib (Nexavar) for the treatment of hepatocellular cancer (HCC).
The Phase Ib trial is a dose escalation study of OMP-54F28 in combination with sorafenib to treat patients with first-line locally advanced or metastatic HCC.
The primary objectives are to assess the safety of the combination regimen and determine a recommended Phase II dose for OMP-54F28 in combination with sorafenib.
Major secondary and exploratory objectives include assessment of the pharmacokinetics (PK) and pharmacodynamics (PD) of OMP-54F28, as well as the efficacy of the combination.
The company said that tumour tissue from patients will be used to explore predictive biomarker hypotheses related to the efficacy of OMP-54F28.
Indiana University in Indianapolis assistant professor of Clinical Medicine Safi Shahda said: "Patients with more advanced disease have very few treatment options.
"OMP-54F28 holds the potential to make a real difference for these patients as it was designed to attack so-called cancer stem cells that can generate new cancer cells and are particularly resistant to currently available cancer drugs."
The company said that the preclinical data suggest that OMP-54F28 adds significant anti-tumour activity to sorafenib by eliminating tumour-initiating cells in models for hepatocellular cancer.
OncoMed chief medical officer Jakob Dupont said: "The safety profile for OMP-54F28 in the single-agent Phase 1 study is favorable, and we will now explore its ability to combine with sorafenib in preparation for future potential randomised studies."
The trial is the second of three Phase Ib studies for OMP-54F28 scheduled to begin patient enrolment in the next few months as part of the company's partnership with Bayer Pharma (Bayer).
Earlier this year, the company started a Phase Ib of OMP-54F28 with nab-paclitaxel (Abraxane) and gemcitabine in pancreatic cancer.
Interim results from the single-agent, first-in-human Phase Ia trial carried out in solid tumour patients demonstrated that OMP-54F28 is well tolerated and modulates the Wnt pathway starting at low doses, as evidenced by pharmacodynamic biomarker analysis of hair follicles.
OncoMed chairman and chief executive officer Paul Hastings said: "With two of three Phase 1b combination clinical studies now underway for OMP-54F28, and the initiation of all three planned Phase 1b studies for vantictumab late last year, we are very close to achieving that objective," Hastings added.
"Data generated from these studies will provide the basis for Bayer to exercise their option to license OMP-54F28 and vantictumab and the trials will also serve to inform future Phase 2 clinical studies of these novel drug candidates."
Image: Intermediate magnification micrograph of hepatocellular carcinoma the most common form of primary liver cancer. Photo: courtesy of Nephron.