OncoMed Pharmaceuticals has been given the green light to continue recruiting patients for its Phase 1b clinical trial of vantictumab (OMP-18R5) to treat breast cancer patients. The Food and Drug Administration had placed a partial clinical hold on enrollment for the trial following OncoMed’s voluntary halt due to concerns over adverse effects.
“We are pleased by the FDA’s action to allow the resumption of enrollment in the vantictumab clinical trials,” said Jakob Dupont, MD, Chief Medical Officer of OncoMed, in a news release from the company. “Patient safety is our top priority.”
Patients were experiencing on-target mild-to-moderate bone-related adverse events while using vantictumab. This is likely a result of vantictumab being in the class of Wnt pathway inhibitors. While inhibiting the Wnt pathway has been shown to fight cancer stem cell and tumor activity in patient-derived xenograft tumor models, the Wnt pathway is also vital to normal bone development and maintains bone health throughout life. Inhibiting the Wnt pathway–in this case, inhibiting Frizzled7, an activator of Wnt signaling–may have negative effects on bone health.
To mitigate these risks, OncoMed modified dosing regimens, increased bone monitoring and protection, and modified enrollment criteria for the study. “The revised protocols were developed with input from the vantictumab clinical investigators and academic bone experts and are intended to mitigate the risks of future adverse events as we seek an optimal and efficacious dose to take forward in the development of this first-in-class Wnt pathway inhibitor,” said Dr. Dupont.
In addition to the trial treating advanced HER2-negative breast cancer patients, a trial treating non-small cell lung cancer patients and a trial treating stage IV pancreatic cancer patients are returning to recruitment efforts. These three different cancer types have the potential to be treated with vantictumab because vantictumab has broad effects on tumor types. Phase 1a studies of patients with advanced solid tumors were presented in 2013 at the European Cancer Conference in the Netherlands. Positive results led to the initiation of the present phase 1b studies. Bayer Pharma is interested in the vantictumab trials and has formed a strategic alliance with OncoMed.
“The diligence and dedication of OncoMed’s clinical development team to temporarily halt the vantictumab studies and submit a comprehensive response to the FDA has led to a prompt action by the agency,” said Paul J. Hastings, Chairman and Chief Executive Officer of OncoMed. “We look forward to proceeding with the vantictumab Phase 1b clinical studies, and to the potential opt in by our partner Bayer based on data from these trials, to realize the future potential of this novel first-in-class WNT pathway inhibitor.”