AVEO Oncology, a Cambridge, Mass.-based cancer therapeutics company, and Astellas Pharma, A Tokyo-based a pharmaceutical company, have initiated patient enrollment in a phase II trial evaluating the efficacy of tivozanib, an investigational drug, in combination with paclitaxel in patients with locally recurrent or metastatic triple negative breast cancer.

The study, named BATON-BC, will be a randomized, double-blind, multi-center trial and will enroll approximately 147 patients with triple negative breast cancer who have received no prior systemic therapy for advanced or metastatic breast cancer (mBC). Triple negative breast cancer was selected for tivozanib clinical evaluation because of high unmet need and insights gained from AVEO’s Human Response Platform indicating that these tumors are enriched for a signature of VEGF pathway deregulation similar to that seen in renal cell carcinoma (RCC). BATON-BC is the third trial to be initiated as part of the BATON clinical development program, which includes ongoing trials in advanced metastatic colorectal cancer and advanced RCC.

“While currently available chemotherapy and hormonal therapies have significantly enhanced the survival of women diagnosed with breast cancer, there remains an unmet treatment need for those fighting advanced triple negative breast cancer,” said Erica Mayer, M.D., M.P.H., director of clinical research, Dana-Farber/Brigham and Women’s Cancer Center at Faulkner Hospital, and BATON-BC primary investigator. “The BATON-BC trial is designed to evaluate progression-free survival as well as improve our understanding of triple negative breast cancer by providing us with the opportunity to identify the patients who are most likely to be responsive or resistant to tivozanib therapy.”

The primary endpoint of BATON-BC is progression-free survival (PFS). Secondary objectives include evaluation of objective response rate, overall survival and safety. An additional component of BATON-BC is the evaluation of biomarker relationships that may be predictive of clinical response to tivozanib in patients with triple negative breast cancer.

“While tivozanib is currently under review with the FDA for advanced RCC, we’re committed to investigating the development of tivozanib beyond advanced RCC,” said Stephen Eck, M.D., Ph.D., vice president of medical oncology, Astellas Pharma Global Development.

Data from a phase Ib clinical trial of tivozanib (0.5mg - 1.5mg per day for three weeks, followed by one week off, repeating at a cycle of 28 days) in combination with weekly paclitaxel (three weeks on, followed by one week off) in patients with metastatic breast cancer demonstrated that the combination was considered tolerable at the full dose and schedule of both agents (tivozanib 1.5mg and paclitaxel 90mg/m²), and resulted in an objective response rate of 38% (5/13 patients). In the study, 54% (7/13) of patients had stable disease (SD), with a median duration of SD of 8.5 months (range: 4.2–10.7).¹

“Currently there are no approved targeted therapies for the treatment of triple negative breast cancer. Biomarkers derived from AVEO’s Human Response Platform will be evaluated for potential use in identifying breast cancer patients who will be most likely to benefit from treatment with tivozanib,” said William Slichenmyer, M.D., Sc.M., chief medical officer at AVEO. “Following the FDA’s recent acceptance of a New Drug Application seeking approval for tivozanib in advanced RCC, we remain committed to expanding the development of tivozanib in additional solid tumor types, and look forward to further evaluating tivozanib as a potential new treatment option for patients living with triple negative breast cancer.”