BZL101 is an oral drug designed for the treatment of advanced breast cancer with a novel mechanism of action. BZL101 targets diseased cells while leaving normal cells healthy and intact. Normal cells depend primarily on the citric acid cycle (>85%) and very little on glycolysis (<7%) for energy production. In contrast, cancer cells depend largely on glycolysis (>85%) for energy production. BZL101 stops the production cycle of energy in cancer cells by inhibiting glycolysis. This leads to DNA damage and cancer cell death while normal cells remain unharmed.
Antiproliferative Activity
BZL101 was evaluated for antiproliferative activity on five breast cancer cell lines (SK-BR-3, MCF7, MDA-MB-231, BT-474, and MCNeuA). BZL101 showed >50% growth inhibition on a panel of breast, lung, prostate and pancreatic cancer cell lines. BZL101 at the same dose did not cause >25% of growth inhibition on normal human mammary cells (HuMEC), demonstrating selectivity to cancer cells. BZL101 was also orally active in preventing tumor formation in a mouse xenograph model.
Phase 1 Clinical Results
Bionovo’s lead cancer candidate has been evaluated in two Phase 1 clinical trials and a total of 47 women with advanced breast cancer have been treated with BZL101. Data from the Phase 1 clinical trials of BZL101 indicate the drug is well tolerated and safe for clinical use.
Next Steps: Phase 2 Clinical Trial
A multi-center, Phase 2, open-label, non-randomized clinical trial to assess ongoing safety and preliminary efficacy of BZL101 for the treatment of metastatic breast cancer is being conducted under the directorship of Dr. Charles L. Shapiro at the Ohio State University Medical Center. Once a maximum tolerated dose is determined from the second Phase 1, dose escalation trial, a total of 80 women with histologically confirmed breast cancer and measurable stage IV disease will be enrolled to the Phase 2 trial. Of the 80 women, 40 will have hormone receptor-positive disease and 40 will have hormone receptor-negative disease. The primary outcome measure will be response to therapy evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST). Secondary measures of efficacy will include: duration of overall objective response, progression-free survival, overall survival, and patient reported quality of life measures. Recruitment for the clinical trial is taking place at 17 clinical sites throughout the United States.
Click here to visit Bionovo's BZL101 clinical trial website.
About the Principal Investigator
Dr. Charles L. Shapiro is an Associate Professor of Internal Medicine in the Division of Hematology/Oncology. He is the Director of Breast Medical Oncology, Co-Director of the Comprehensive Breast Health Services, and Director of the Lance Armstrong Center of Excellence at Ohio State University Medical Center (OSUMC) and Comprehensive Cancer Center (CCC). Dr. Shapiro’s research interests are focused on the long-term side effects of adjuvant therapy, and the development of novel therapies for breast cancer. In particular, he has studied anthracycline-related cardiac effects and the impact of chemotherapy-induced ovarian failure on skeletal health in young women. He is currently the principal investigator on a randomized Cancer and Leukemia Group B (CALGB) trial evaluating zolendronic acid in women with chemotherapy-induced ovarian failure. He also serves as principal investigator on a number of investigator-initiated trials in advanced breast cancer combining taxanes with biological agents including bortezomib, bevacizumab, and low-dose suramin. Dr. Shapiro is the Director of the Clinical Scientific Review Committee for the OSUCCC, and the Chair of the Symptom Intervention Committee of the CALGB. In addition, he co-chairs the ASCO Committee on adult survivorship guidelines, and has been appointed to the newly formed NCI Symptom Management and Health-Related Quality of Life Steering Committee.
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