Disease Background and Scientific Rationale

The American Cancer Society (ACS) reports that among American women, breast cancer is the most common form of cancer, second only to skin cancers. The ACS estimates that approximately 182,000 new cases of breast cancer were diagnosed in the United States in 2008. Statistically, one in eight women will be diagnosed with invasive breast cancer in her lifetime.

There are many types of breast cancer. In recent years, advances in diagnostic testing have enabled physicians to more accurately categorize the types of breast cancer and therefore make more strategic treatment decisions. One particular type of cancer is HER2 positive (HER2+) breast cancer, which positively tests for a gene called human epidermal growth factor receptor-2 (HER2). All humans have this gene in their genetic makeup, as it plays a role in the regulation of cell growth; however, patients with HER2+ breast cancer have many copies of the gene causing tumor cells to grow faster than usual. A surplus of copies, or overexpression of the gene, typically indicates a more aggressive subtype of breast cancer that may have a poor response to hormone treatment or chemotherapy alone.

Treatment of HER2+ breast cancer is based on several factors including the type and stage of the cancer, how sensitive the cancer is to specific hormones, and whether or not the HER2 gene is overexpressed. Generally, breast cancer treatment can include chemotherapy, radiation therapy, and/or surgery (lumpectomy or mastectomy). Additional treatments could include hormone therapy that blocks the hormones that stimulate cancer growth and/or targeted therapy to block the HER2 cancer cell growth.

Patients who have an overexpression of the HER2 gene are often treated with medications that specifically target HER2 in addition to standard chemotherapy. By targeting the HER2 gene, the cancer cells are killed and the risk of recurrence is reduced. While there are available targeted treatments on the market today, HER2+ breast cancer remains a difficult disease to treat as many HER2+ patients experience recurrence underscoring the need for more advanced treatments that can be used alone and/or in combination with current treatment options.

Phase 2 Clinical Trial

In 2009, Infinity initiated a Phase 2 clinical trial of IPI-504, its lead heat shock protein 90 (Hsp90) chaperone inhibitor, in HER2+ metastatic breast cancer, in combination with Herceptin® (trastuzumab), a targeted cancer therapy commonly used to treat HER2+ breast cancer. In preclinical studies, IPI-504 has demonstrated the potential to disrupt the activity of multiple proteins and cell signaling pathways implicated in tumor growth, including HER2, a key signaling pathway in breast cancer.

The goal of the Phase 2 trial is to evaluate the safety and anti-tumor activity of IPI-504 in combination with Herceptin in patients with pretreated, locally advanced metastatic HER2+ breast cancer.