US-based OncoMed Pharmaceuticals has started dosing in the randomised, double-blind, placebo-controlled Phase II clinical trial (YOSEMITE) of demcizumab (anti-DLL4, OMP-21M18) in patients with first-line metastatic pancreatic cancer.
Demcizumab is a humanised monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in the Notch signaling pathway.
The company is developing new therapeutics that target cancer stem cells (CSCs) or tumour-initiating cells.
The YOSEMITE trial will compare the efficacy and safety of demcizumab combined with standard of care Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in patients with first-line metastatic pancreatic cancer.
The trial’s primary endpoint is progression-free survival (PFS), while secondary endpoints include overall survival, response rate, duration of response, safety, immunogenicity and pharmacokinetics.
Around 200 patients will be enrolled in the trial, which is being conducted at about 50 centres in the US, Canada, Europe and Australia.
In the three-arm trial, patients in arm one will receive Abraxane plus gemcitabine plus placebo, while those in the second arm will receive standard of care plus one course of demcizumab 3.5mg/kg every two weeks for 70 days.
Patients in the third arm will receive standard of care plus a second course of demcizumab following a 100-day wash out period.
OncoMed chief medical officer Dr Jakob Dupont said: "Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and Europe and continues to represent a high unmet medical need.
"Our aim with the Phase II YOSEMITE trial is to assess the potential of enhancing patient benefit by adding demcizumab to the current standard of care of Abraxane plus gemcitabine."
Demcizumab is being developed as part of OncoMed’s collaboration with Celgene Corporation.
Under this deal, OncoMed is eligible to get a $70m milestone from Celgene for successful completion of an interim safety analysis associated with the two randomised demcizumab Phase II trials (YOSEMITE and the DENALI non-small cell lung cancer trial).
OncoMed chairman and chief executive officer Paul Hastings said: "With the start of this second randomised Phase II clinical trial for demcizumab, OncoMed is now enrolling patients in four randomised Phase II proof-of-concept trials.
"Data from multiple randomised Phase II trials is expected to be available in the 2016-2017 timeframe."
Image: Histopathogic image of pancreatic adenocarcinoma arising in the pancreas head region. Photo: courtesy of user:KGH.