AVEO Oncology, a cancer therapeutics company, and Astellas Pharma Inc.,a pharmaceutical company dedicated to improving the health of people around the world, have initiated patient enrollment in a randomized, double-blind, multi-centre phase II clinical trial, called BATON-BC, evaluating the efficacy of tivozanib, an investigational drug, in combination with paclitaxel compared to placebo in combination with paclitaxel in patients with locally recurrent or metastatic 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 PlatformTM 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 (Biomarker Assessment of Tivozanib in ONcology) 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, MD, MPH, director of Clinical Research, Dana-Farber/Brigham and Women’s Cancer Centre at Faulkner Hospital, assistant professor in medicine, Harvard Medical School, 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.”

BATON-BC, which is being led by AVEO, is a double-blind, placebo-controlled, randomized (2:1 tivozanib/placebo), multi-centre study that will enroll approximately 147 patients at 50 sites worldwide. 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, MD, PhD., vice president of Medical Oncology, Astellas Pharma Global Development. “At Astellas, we are committed to discover and develop molecularly targeted therapies and precision medicines that have the potential to revolutionize the methods used to treat cancer patients.”

Data from a phase I b clinical trial of tivozanib (0.5 mg - 1.5 mg 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 1.5 mg and paclitaxel 90 mg/m2), and resulted in an objective response rate of 38 per cent (5/13 patients). In the study, 54 per cent (7/13) of patients had stable disease (SD), with a median duration of SD of 8.5 months (range: 4.2–10.7).

“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, MD, 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.”

Globally, breast cancer is diagnosed in about millions of women annually. Triple negative breast cancer is comprised of tumours that do not express the estrogen receptor, progesterone receptor or the human epidermal growth factor receptor-2 and accounts for approximately 12-20 per cent of breast cancers. Receptor expression is typically confirmed at the time of a breast cancer diagnosis. There are currently no approved targeted therapies for triple negative breast cancer.

Tivozanib is a potent, selective and long half-life inhibitor of all three vascular endothelial growth factor (VEGF) receptors that is designed to optimize VEGF blockade while minimizing off-target toxicities. Tivozanib is an oral, once-daily, investigational tyrosine kinase inhibitor for which positive results from a phase III clinical study in advanced RCC have been reported, and is being evaluated in other tumours.

BATON-BC is a double-blind, placebo-controlled, randomized (2:1 tivozanib/placebo), multicenter study that will enroll approximately 147 patients at 50 sites worldwide. The trial compares PFS of triple negative breast cancer patients treated with tivozanib in combination with paclitaxel versus placebo in combination with paclitaxel. Secondary objectives include evaluation of objective response rate, overall survival and safety. Additional exploratory objectives include the evaluation of potential tumor biomarkers predictive of tumor sensitivity and/or resistance to tivozanib in combination with paclitaxel and effectiveness of tivozanib in combination with paclitaxel in defined intrinsic molecular breast cancer subtypes.

In February 2011, AVEO and Astellas entered into a worldwide agreement to develop and commercialise tivozanib outside of Asia for the treatment of a broad range of cancers. Tivozanib, AVEO's lead investigational drug, is a potent, selective, long half-life inhibitor of all three VEGF receptors that is designed to optimize VEGF blockade while minimizing off-target toxicities. Subject to regulatory approval, AVEO will lead commercialization of tivozanib in North America and Astellas will lead commercialisation of tivozanib in the European Union (EU).