Cell Therapeutics, Inc. has announced that the North Central Cancer Treatment Group (NCCTG) plans to conduct a Phase II study of brostallicin in combination with cisplatin in patients with metastatic triple-negative breast (mTNBC) cancer, defined by tumors lacking expression of estrogen, progesterone receptors and without over-expression of HER2.
Additionally, the majority of breast cancers that are associated with the susceptibility mutation (BRCA1) are of the triple-negative type. BRCA1 is a tumor suppressor gene which, when mutated, is associated with the development of hereditary breast cancers. Changes in the BRCA1 status can make tumors rapidly acquire resistance to chemotherapy requiring development of new agents to effectively treat these patients. Brostallicin is a novel synthetic second-generation DNA minor groove binder with enhanced efficacy in the presence of the BRCA1 mutation and has demonstrated synergy in combination with cisplatin, an active therapeutic for this disease.
Brostallicin has also demonstrated a unique ability to retain activity in tumors that are resistant to other cancer drugs (Mol Cancer Ther 2009; 8(7) July 2009; 1985-94). Women with mTNBC have very limited effective treatments and based on the novel mechanism of action of brostallicin and the recognized activity of cisplatin in this disease, the combination of the two agents will be explored by the NCCTG.
In addition to standard clinical efficacy measures, biological endpoints will also be evaluated to assist in understanding the specific activity of the therapeutic in this disease.
"As we determine the underlying genetic background of disease, we believe we will be able to select the appropriate patients for testing of novel agents such as brostallicin. In the development of brostallicin, studies have indicated significant responses in particular genetic backgrounds (one being triple negative breast cancer)," said Christina Waters, Ph.D., MBA, President of CTI Europe and Systems Medicine, LLC and former Director of Scientific Development at Genomics Institute of the Novartis Research Foundation. "We are moving to a more sophisticated clinical treatment paradigm, from general cell ablation to targeted therapy, which we believe will improve patient response in select populations and decrease exposure to patients that cannot respond."
The demonstration of tumor sensitization to brostallicin in the presence of BRCA1 suppression was completed in collaboration with Translational Genomics Research Institute (TGEN) and Systems Medicine, LLC a wholly-owned subsidiary of the Company.