Cedars-Sinai has been chosen to participate in a Phase 1b clinical trial of an antibody that targets breast cancer by attacking special cells that drive tumor growth and metastasis. The antibody, known as vantictumab, is being explored for its potential to improve treatment of patients with advanced breast cancer.
Monica Mita, MD, associate professor of medicine and co-director of the Experimental Therapeutics Program at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, is the principal investigator for the portion of the clinical trial to be conducted at Cedars-Sinai. The two other sites for the multi-center study are Baylor Sammons Cancer Center – The US Oncology Network, Dallas, and The US Oncology Network, Tyler, Texas.
OncoMed Pharmaceuticals Inc. of Redwood City, Calif., is directing the Phase 1b clinical trial, the first of three it expects to launch for vantictumab in collaboration with Bayer Pharma AG, according to an Oct. 29 news release from the company. The antibody targets cancer stem cells, also known as tumor-initiating cells, along with bulk tumor cells. In the clinical trial, it will be administered in conjunction with paclitaxel, a standard chemotherapy, to patients with locally advanced or metastatic HER2 negative breast cancer.
The primary objectives of the Phase 1b clinical trial are "to evaluate safety of this combination regimen and determine a recommended Phase 2 dose for vantictumab in combination with paclitaxel," the news release said. It added that secondary and exploratory objectives include evaluating the pharmacokinetics – absorption, metabolism and excretion – of vantictumab, as well as the efficacy of this combination.
At Cedars-Sinai, Mita said she expects to enroll a small group of patients with advanced breast cancer. In the long run, she said, she hopes that the dual regimen of vantictumab and paclitaxel may improve the response rate to treatment for patients with metastatic breast cancer.
So far, OncoMed Pharmaceuticals said, vantictumab has shown anti-stem cell and anti-tumor activity in xenograft tumor models derived from patients. The antibody inhibits a key signaling pathway in cancer, the Wnt pathway. Its effect on cancer stem cells (CSCs) is of particular interest because these cells can differentiate into other cells that form the bulk of the tumor.
"Common cancer drugs target bulk tumor cells but have limited impact on CSCs, thereby providing a path for recurrence of the tumor," OncoMed said in its news release. "OncoMed's product candidates target CSCs by blocking self-renewal and driving differentiation of CSCs toward a non-tumorigenic state, and also impact bulk tumor cells."
The Cedars-Sinai Experimental Therapeutics Program is designed to offer an array of research options to cancer patients when standard options are not available. Most studies that it conducts are Phase I clinical trials, which screen potential drug treatments for safety and dosage levels. Founded in January 2012 by Monica Mita and co-director Alain Mita, MD, the program has expanded rapidly.