Pancreatic cancer

OncoMed Pharmaceuticals has initiated a Phase Ib clinical trial of its Wnt-pathway-targeting antibody vantictumab (OMP-18R5) in combination with nab-paclitaxel (Abraxane) and gemcitabine in patients with Stage IV pancreatic cancer.

The new trial is the last of the three Phase Ib trials for vantictumab that the company started in this year as part of its collaboration with Bayer Pharma.

OncoMed chief medical officer Jakob Dupont said the Wnt signalling pathway is implicated to be central to cancer stem cells survival and potentially a major therapeutic target in pancreatic cancer.

"Our Wnt pathway targeting antibody, vantictumab, reveals impressive preclinical data efficacy data in combination with gemcitabine and Abraxane in OncoMed’s minimally passaged patient-derived pancreatic cancer models," Dupont said.

The multi-centre, dose escalation Phase Ib trial is aimed at assessing the safety of vantictumab in combination with Abraxane and gemcitabine, as well as to determine a recommended Phase II dose for the combination treatment.

The secondary and exploratory objectives of the study include assessment of the pharmacokinetics (PK) of vantictumab, as well as the pharmacodynamics (PD) and efficacy of the combination.

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In the trial, tumour tissue from patients will be used to explore predictive biomarker hypotheses related to the efficacy of vantictumab.

Indiana University assistant professor of Clinical Medicine Safi Shahda said incidence of pancreatic cancer has been steadily rising.

"By targeting cancer stem cells, vantictumab has the potential to augment the clinical benefit of standard chemotherapy in this disease setting."

"In spite of recent advancements, metastatic pancreatic cancer represents a significant unmet medical need and patients are in need of improved treatment options," Shahda said.

"By targeting cancer stem cells, vantictumab has the potential to augment the clinical benefit of standard chemotherapy in this disease setting."

Vantictumab, a first-in-class antibody that has shown broad anti-CSC and anti-tumour activity in patient-derived xenograft tumour models, inhibits the Wnt pathway, a key signalling pathway in cancer.

OncoMed chairman and chief executive officer Paul Hastings said: "The clinical data from these three trials will yield important clinical information about this novel anti-cancer stem cell agent in the key solid tumour indications of non-small cell lung, breast and pancreatic cancer and may also lead to an opt-in decision by Bayer to take vantictumab into late-stage randomised clinical trials."

OncoMed is currently completing a Phase Ia study of vantictumab in patients with advanced solid tumours, the preliminary data of which were presented at the European Cancer Conference in September in Amsterdam, Netherlands.

Image: Histopathogic image of pancreatic adenocarcinoma arising in the pancreas head region. Photo: courtesy of KGH.