"This Phase III trial is an important milestone in our development of Nexavar as it provides an opportunity to validate the promising Phase II results," said Dr. Dimitris Voliotis, Vice President, Global Clinical Development Oncology, Bayer HealthCare. "We look forward to continuing our breast cancer clinical trial program, which includes support of two ongoing cooperative group-sponsored Phase II trials, to gain additional understanding of how Nexavar may play a role in the advanced breast cancer treatment paradigm."
Phase III Trial Design
The RESILIENCE (Phase III TRial Comparing CapecitabinE in Combination with SorafenIb or PLacebo for Treatment of Locally Advanced or MetastatIc HER2-Negative Breast CancEr) trial is a randomized, double-blind, placebo-controlled Phase III study planned to enroll 519 patients in more than 20 countries, including the United States, Brazil, Japan and Australia. The study will evaluate Nexavar in combination with capecitabine in patients with locally advanced or metastatic HER-2 negative breast cancer who are resistant to or have failed prior taxane and an anthracycline or for whom further anthracycline is not indicated.
The primary endpoint of the study is progression-free survival. Secondary endpoints include overall survival, time to progression, and safety. Patients will receive 600 mg of oral Nexavar or matching placebo daily on a continuous schedule, in addition to 1000mg/m2 of capecitabine twice daily for 14 days of a 21 day cycle. Dose escalation to 800 mg of oral Nexavar daily and capecitabine 1250 mg/m2 twice daily will be permitted depending on tolerance.
"Nexavar has demonstrated efficacy in advanced kidney cancer and unresectable liver cancer, and Bayer and Onyx are hopeful that this Phase III trial will lead to a new treatment option for patients with advanced breast cancer," said Ted W. Love, M.D., Executive Vice President and Head of Research and Development for Onyx Pharmaceuticals. "We are committed to evaluating Nexavar's full potential in a variety of treatment settings and tumor types."
Phase II Trial results
Results from the Phase II trial combining Nexavar with capecitabine were presented in 2009 by Jose Baselga, M.D., chairman and professor of medicine at Vall d'Hebron Institute of Oncology in Barcelona and the principle investigator of the study, at the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress and the 32nd Annual San Antonio Breast Cancer Symposium (SABCS). Patients receiving Nexavar plus capecitabine (N=115) had a 74 percent improvement in the time they lived without their disease progressing compared to those who received chemotherapy alone (N=114). The difference in median progression-free survival of Nexavar plus capecitabine versus capecitabine plus placebo was statistically significant, 6.4 months vs. 4.1 months (HR=0.576, p=0.0006). Overall, treatment with capecitabine plus Nexavar did not result in any new side effects. Common grade 3 treatment-related adverse events included hand-foot skin reaction (45%), diarrhea (5%), dyspnea (5%), neutropenia (4%) and mucositis (1%).
About the Nexavar Clinical Program in Breast Cancer
In a cooperative group-sponsored clinical development program known as Trials to Investigate the Effects of Sorafenib in Breast Cancer (TIES), Nexavar is being evaluated in a variety of treatment settings for patients with breast cancer by investigators and oncology cooperative groups. Among these clinical trials are two ongoing randomized Phase II studies, including a trial to evaluate Nexavar plus gemcitabine or capecitabine in the second-line setting following progression on bevacizumab, and a trial to evaluate Nexavar plus docetaxel and/or letrozole in the first-line metastatic breast cancer setting.
About Breast Cancer
Breast cancer was the most commonly diagnosed cancer among women worldwide in 2007-2008 (approximately 1.3 million cases), and the second leading cause of cancer-related death among women (approximately 465,000 deaths). It is the most commonly diagnosed cancer among women in the United States (1 in 4 cancer diagnoses is breast cancer). There are approximately 200,000 new cases of breast cancer in the United States and 430,000 in Europe each year. More than 40,000 women in the United States and more than 130,000 in Europe die of breast cancer each year.
Nexavar®, an oral anti-cancer therapy, is currently approved in 100 countries for liver cancer where it remains the only approved systemic agent proven to extend survival and in 100 countries for the treatment of patients with advanced kidney cancer. In Europe, Nexavar is approved for the treatment of hepatocellular carcinoma and for the treatment of patients with advanced renal cell carcinoma (RCC) who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy.
Nexavar inhibits processes involved in both the tumor cell and tumor vasculature. In preclinical studies, Nexavar has been shown to target members of two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply) - two important processes that enable cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR B, KIT, FLT-3 and RET.
Nexavar is also being evaluated by the companies, international study groups, government agencies and individual investigators as a single agent or combination treatment in a range of cancers, including lung, thyroid, ovarian and colorectal cancer and as an adjuvant therapy for liver and kidney cancer.
About Onyx Pharmaceuticals, Inc.
Onyx Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of people with cancer. The company, in collaboration with Bayer HealthCare Pharmaceuticals Inc., is developing and marketing Nexavar® (sorafenib) tablets, a small molecule drug that is currently approved for the treatment of liver cancer and advanced kidney cancer. Additionally, Nexavar is being investigated in several ongoing trials in a variety of tumor types. Beyond Nexavar, Onyx has established a development pipeline of anticancer compounds at various stages of clinical testing, including carfilzomib, a selective proteasome inhibitor, that is currently being evaluated in multiple clinical trials for the treatment of patients with relapsed or relapsed/refractory multiple myeloma and solid tumors. ONX 0801, an alpha-folate receptor targeted inhibitor of thymidylate synthase, and ONX 0912, an oral proteasome inhibitor, are currently in Phase 1 testing.
About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of EUR 15,988 million (2009), is one of the world's leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer HealthCare's aim is to discover and manufacture products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 53.400 employees and is represented in more than 100 countries.