Abstract OT2-3-06: A phase II, non-randomized, multicenter, exploratory trial of single agent BKM120 in patients with triple-negative metastatic breast cancer.
Authors: Saura C , Lin N , Ciruelos E , Maurer M , Lluch A , Gavilá J , Winer E , Baselga J , Rodón J 
Published: August 2014

Abstract
Despite best available therapy, triple-negative breast cancer (TNBC) continues to be associated with poorer outcomes when compared to other breast cancer subtypes and poses a serious therapeutic challenge. Therefore, novel and more efficacious therapies are in great need. It is widely accepted nowadays, that TNBC is not homogeneous, but comprised of a number of subpopulations very different in genetic make-up, oncogene dependence, and response to treatment. Among these, multiple core phosphatidylinositol-3-kinase (PI3K) pathway components are known to be altered in TNBC. The relevance of activating mutations in the PI3KCA gene or PTEN/INPP4B loss of protein expression on the virulence of breast cancer and response to PI3K inhibitors is yet to be elucidated. PI3K hyperactivity due to these alterations suggests that inhibitors of the PI3K pathway may be used to reverse resistance.
BKM120 is a potent and highly specific oral pan-class I PI3K inhibitor currently in clinical development. This non-randomized, two-stage, open-label, single-arm exploratory trial is designed to elucidate the preliminary therapeutic value of BKM120 in patients with metastatic TNBC and to identify subpopulations that may mostly benefit. Women 18 years and above with confirmed mTNBC who have received at least two prior chemotherapy regimens in the adjuvant or metastatic setting are eligible to participate. Availability of a tumor block from the primary tumor or accessible metastasis for biopsy is mandatory. The primary objective is to determine the clinical activity of BKM120 defined as the clinical benefit rate (CR, PR or SD for more than 4 months per RECIST 1.1). Secondary objectives are to determine progression-free survival, overall survival, safety profile, pharmacodynamic effects, and to identify biomarkers predictive of response. BKM120 will be administered orally at a 100-mg dose, once daily, in a continuous schedule. Treatment will continue until disease progression, unacceptable toxicity, or decision of the physician or the patient to terminate participation.
Stage 1 will include up to 50 patients with an intermediate analysis after the enrollment of the first 29 subjects. If no sufficient activity is observed, the clinical trial will be terminated. If drug activity is observed, enrollment will continue up Stage 1 completion. After 50 patients are enrolled, a comprehensive analysis of molecular markers using technology and knowledge gathered in the Stand Up to Cancer Dream Team will take place. This analysis will be focused in identifying molecular markers predictive of response that would guide patient selection for Stage 2. Two clone investigator-initiated protocols (one for the US, one for Spain) are enrolling in parallel. A total of 110 patients will take part in this study in four sites in Spain and in 2 in the US: 50 patients in Stage 1 and 60 in Stage 2, exploring a maximum of 3 subgroups of 20 patients each. The trial is funded by a Stand Up to Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0209) and supported by Novartis. Patient enrollment started in June 2012.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-3-06.