BSI-201, progresses as planned with the Phase 3 study meeting expectations on patient accrual and trial site coverage in the United States. Study investigators have enrolled 214 of the target number of 420 patients.
BSI-201 entered a Phase 3 clinical trial in the United States in July 2009 and is being evaluated in combination with chemotherapy in patients with mTNBC, a condition defined by tumors lacking expression of estrogen, progesterone receptors and without overexpression of HER2. BSI-201 is a novel investigational targeted therapy that inhibits poly (ADP-ribose) polymerase (PARP1), an enzyme involved in DNA damage repair.
The decision to commence with the Phase 3 study in July was based on the encouraging Phase 2 study results presented at ASCO on May 31, 2009. In the Phase 2 clinical trial, women with mTNBC who were randomly assigned to receive gemcitabine and carboplatin (GC) in combination with the investigational agent BSI-201 or GC alone. Updated Phase 2 data including overall survival were presented, Friday, December 11, at 5:30 pm CST, at a poster session at the 32nd Annual San Antonio Breast Cancer Symposium (SABCS).
The addition of BSI-201 to GC improved median overall survival from 7.7 months to 12.2 months. (HR=0.5, p=0.005). BSI-201 did not add to the frequency or severity of adverse events associated with chemotherapy. This is not a final analysis of the Phase 2 data, but rather an updated analysis of overall survival. Median survival has not yet been reached in the BSI-201 arm, therefore the data cut-off period for the Phase 2 trial from September to November.
“The updated analysis from the Phase 2 program, including data on overall survival, are consistent with the positive results presented earlier this year at ASCO,” declared Marc Cluzel, Executive Vice President, R&D, sanofi-aventis. “We are very encouraged by the fast recruitment of patients in Phase 3 trial. We hope the findings will lead to emerging strategy that may help women with metastatic triple negative breast cancer.”
The U.S. Food and Drug Administration (FDA) granted Fast Track designation to BSI-201 for mTNBC. As described by the FDA, the Fast Track process is designed to expedite the review of drugs being developed for serious diseases with the potential to address an unmet medical need.
About the BSI-201 Phase 3 Trial
The Phase 3 trial is a multi-center, randomized trial designed to evaluate the safety and efficacy of BSI-201 when combined with gemcitabine and carboplatin (GC) in women with mTNBC. A total of 420 mTNBC patients, who have received 0-2 prior therapies in the metastatic setting will be randomized to receive GC with or without BSI-201.
The co-primary objectives of the Phase 3 study are to assess improvement in progression-free survival and overall survival. The secondary objectives are to assess objective response rate and safety. The trial encompasses an estimated 94 sites in the United States. Importantly, this trial will have a crossover provision that will ensure that all patients enrolled in the BSI-201 Phase 3 clinical trial have the potential opportunity to receive BSI-201 (patients randomly assigned to the control arm may receive BSI-201 upon disease progression).
About BSI-201
BSI-201 is a potential first-in-class investigational targeted therapy designed to inhibit poly (ADPribose) polymerase (PARP1), an enzyme involved in DNA damage repair. Among other investigational PARP inhibitors in the industry, BSI-201 is the farthest along in clinical development in the mTNBC setting. BSI-201 is currently being evaluated for its potential to enhance the effect of chemotherapy-induced DNA damage on cancer cells where PARP hyperactivity was demonstrated. BSI-201 is in Phase 3 for mTNBC, as well as in Phase 2 trials in patients with ovarian, uterine, brain and lung cancers.
About Triple-Negative Breast Cancer
When patients are diagnosed with breast cancer, their tumors are routinely tested for the presence of estrogen and progesterone receptors and for the over-expression of HER2. Commonly used breast cancer therapies target these receptors; for example, tamoxifen for estrogen receptor and trastuzumab for HER2. However, 15-20 percent of all breast cancers lack over-expression of all three proteins, thus giving rise to the term “triple-negative breast cancer” or “TNBC.”
TNBC can be an aggressive disease, with higher rates of metastases and poorer survival rates than other breast cancer subtypes. No treatment has been approved specifically for TNBC.