Study of LEE011 With Fulvestrant and BYL719 or BKM120 in Advanced Breast Cancer

A Phase Ib/II Study of LEE011 in Combination With Fulvestrant and BYL719 or BKM120 in the Treatment of Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Locally Recurrent or Advanced Metastatic Breast Cancer

The purpose of this trial is to explore the clinical utility of the three investigational agents in HR+, HER2- breast cancer. LEE011 (CDK4/6 inhibitor), BKM120 (PI3K-pan class I-inhibitor) and BYL719 (PI3K-alpha specific class I inhibitor) in combination with fulvestrant.

This is a multi-center, open-label Phase Ib/II study. The Phase Ib portion of the study is a dose escalation to estimate the MTD and/or RP2D for three regimens: LEE011 with fulvestrant; LEE011 and BKM120 with fulvestrant; LEE011and BYL719 with fulvestrant.

The Phase II portion of the study was planned to be a randomized study to assess the anti-tumor activity as well as safety and tolerability of LEE011 with fulvestrant to LEE011 and BKM120 with fulvestrant, and LEE011 and BYL719 with fulvestrant in patients with ER+/HER2- locally advanced or metastatic breast cancer.

Approximately 216 adult women with ER+/HER2- locally advanced or metastatic breast cancer were planned to be enrolled.

On 31-May-2016 Novartis's made the decision decision to not open the Phase II portion of the study, for business reasons. Sufficient data had already been collected and no additional data for the triplet combinations was needed. As a result, the Phase II portion of the trial was not opened.

Inclusion Criteria:

• Postmenopausal, Hormone receptor positive (HR+), HER2 negative breast cancer
• Unlimited number of lines of endocrine therapy and up to two lines of cytotoxic chemotherapy in the metastatic setting (Phase Ib)
• Unlimited number of lines of endocrine therapy and one line of cytotoxic chemotherapy in the metastatic setting (Phase II)

Exclusion Criteria:

• HER2-overexpression in the patient's tumor tissue
• Inadequate bone marrow function or evidence of end-organ damage
• Severe or uncontrolled medical issues
• Diabetes mellitus

Other protocol-defined inclusion/exclusion criteria may apply