OncoMed Pharmaceuticals, Inc., a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumour-initiating cells, has initiated the patient treatment for its third multi-center phase 1b clinical trial of OMP-54F28 (Fzd8-Fc) with carboplatin and paclitaxel in patients with platinum-sensitive ovarian cancer. OMP-54F28 is a first-in-class decoy receptor targeting the Wnt pathway and is part of OncoMed's collaboration with Bayer Pharma AG (Bayer).

With the commencement of this clinical study, all six of OncoMed's planned phase 1b clinical trials for its proprietary Wnt-pathway-targeting compounds, vantictumab (OMP-18R5) and OMP-54F28, are now enrolling patients. Earlier this year OncoMed initiated two separate phase 1b clinical trials of OMP-54F28 with nab-paclitaxel (Abraxane) and gemcitabine in pancreatic cancer, and with sorafenib (Nexavar) in hepatocellular cancer. During the fourth quarter of 2013, OncoMed initiated three Phase 1b trials for its anti-Frizzled antibody, vantictumab; in combination with paclitaxel in breast cancer, with nab-paclitaxel and gemcitabine in pancreatic cancer, and with docetaxel in non-small cell lung cancer.

"With the initiation of our phase 1b study of OMP-54F28 in ovarian cancer, we have now achieved our goal of six open Phase 1b combination trials for our two anti-cancer stem cell clinical candidates that target the Wnt pathway," said Paul J Hastings, OncoMed's chairman and chief executive officer. "Both candidates have demonstrated promising early data and these phase 1b combination studies will provide critical data for Bayer to exercise their option to license OMP-54F28 and vantictumab and for the planning and execution of phase 2 clinical studies."

The phase 1b clinical trial of OMP-54F28 in combination with carboplatin and paclitaxel is a dose-escalation study in patients with recurrent platinum-sensitive ovarian cancer. Primary objectives of the trial are to evaluate safety of this combination regimen and determine a recommended phase 2 dose for OMP-54F28 in combination with carboplatin and paclitaxel. Key secondary and exploratory objectives include evaluation of the pharmacokinetics (PK) and pharmacodynamics (PD) of OMP-54F28, as well as the efficacy of this combination. Tumor tissue from patients will be used to explore predictive biomarker hypotheses related to the efficacy of OMP-54F28.

Scott McMeekin, M.D., Professor of Obstetrics & Gynecology and Virginia Kerley Cade Chair in Cancer Developmental Therapeutics at the Peggy and Charles Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, is the principal investigator who treated the first patient enrolled in this study. Dr. McMeekin commented, "Patients with advanced ovarian cancer can derive significant benefit from standard-of-care chemotherapy but many will inevitably be faced with recurrent or progressive disease. There is ample evidence that the Wnt pathway plays an important role in ovarian cancer recurrence and resistance to treatment. With OMP-54F28, we now have an opportunity to evaluate whether targeting the Wnt pathway can improve outcomes for these patients in the clinic."  

Three additional investigators and clinical sites are participating in this trial: Gina Mantia-Smaldone, M.D., Fox Chase Cancer Center, Philadelphia, PA; Paul Sabbatini, M.D., Memorial Sloan-Kettering Cancer Center, New York, NY; and Nelson Teng, M.D., Stanford University, Palo Alto, CA.

Interim results for the single-agent, first-in-human phase 1a trial for OMP-54F28 in solid tumour patients were presented at the 2013 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston. Results from the phase 1a study showed that OMP-54F28 is well tolerated and modulates the Wnt pathway starting at low doses, as evidenced by PD biomarker analysis of hair follicles.

"Based on the favourable safety profile observed in our Phase 1a clinical study, we look forward to exploring the tolerability and efficacy of OMP-54F28 with carboplatin and paclitaxel. This chemotherapy is an important standard-of-care for many cancer types, including ovarian cancer," said Jakob Dupont, M.D., chief medical officer of OncoMed. This phase 1b study may open several opportunities to explore the efficacy of OMP-54F28 in ovarian cancer as well as in other solid tumours."

OMP-54F28 is a first-in-class fusion protein that has shown broad anti-CSC and anti-tumour activity in patient-derived xenograft tumour models.  OMP-54F28 inhibits a key signalling pathway in cancer, the Wnt pathway.  Specifically, OMP-54F28 consists of the extracellular ligand-binding domain of the Frizzled 8 receptor and the Fc domain of a human IgG1 antibody.  OMP-54F28 selectively binds Wnt ligands, which are activators of Wnt signalling.  OMP-54F28 is currently in phase 1a in patients with refractory solid tumours.  Data from the OMP-54F28 solid tumour trial were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, MA, in October 2013.  Three phase 1b clinical trials of OMP-54F28 are ongoing: one in pancreatic cancer (gemcitabine/nab-paclitaxel + OMP-54F28), one in hepatocellular carcinoma (sorafenib + OMP-54F28), and one in ovarian cancer (carboplatin/paclitaxel + OMP-54F28). OMP-54F28 is part of OncoMed's collaboration with Bayer.

Cancer stem cells, or CSCs, are the subpopulation of cells in a tumour responsible for driving growth and metastasis of the tumour.  CSCs, also known as tumour-initiating cells, exhibit certain properties which include the capacity to divide and give rise to new CSCs via a process called self-renewal and the capacity to differentiate or change into the other cells that form the bulk of the tumour.  Common cancer drugs target bulk tumour cells but have limited impact on CSCs, thereby providing a path for recurrence of the tumour.  OncoMed's product candidates target CSCs by blocking self-renewal and driving differentiation of CSCs toward a non-tumorigenic state, and also impact bulk tumour cells. OncoMed believes its product candidates are distinct from the current generations of chemotherapies and targeted therapies, and have the potential to significantly impact cancer treatment and the clinical outcome of patients with cancer.

OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel therapeutics targeting cancer stem cells.