Phase 1b/2 Study of BKM120 Plus Trastuzumab in Patients With HER2-positive Breast Cancer

Inclusion Criteria:

World Health Organization (WHO) Performance Status of ≤ 2
Patients with HER2+ breast cancer by local laboratory testing (immunohistochemistry [IHC] 3+ staining or fluorescence in situ hybridization [FISH] confirmation for IHC 2+ and 1+)

Documented tumor resistance to trastuzumab:

Recurrence while on trastuzumab or within 12 months since the last infusion for patients who received trastuzumab as adjuvant treatment
Progression while on or within 4 weeks since the last infusion of trastuzumab for patients who received trastuzumab for metastatic disease.

Documented evidence of progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) on trastuzumab-based therapy defined as:

Phase Ib: at any time before study entry
Phase II: within 16 weeks before date of first dosing

Received at least 1 but no more than 4 prior anit-HER2 based regimens including at least 1 regimen containing trastuzumab (adjuvant or neo-adjuvant trastuzumab will be considered as one prior regimen). HER2 directed therapies are defined as comprising trastuzumab, lapatinib, and trastuzumab-DM1 (T-DM1) only.

• Phase II only: trastuzumab, T-DM1 or lapatinib must be part of the most recent line of therapy

Previous lines of cytotoxic chemotherapy:

Phase Ib: no more than 4 lines of cytotoxic chemotherapy
Phase II: no more than 3 lines of cytotoxic chemotherapy

Measurable disease:

Phase Ib: patient has at least one measurable lesion or non-measurable disease as defined per RECIST
Phase II: patient has at least one measureable lesion as defined per RECIST

|| Specific Inclusion Criteria for patients in BM cohorts:

Patient has evidence of progressing brain metastases and/or new metastatic brain lesion(s) without leptomeningeal disease.
Patient has received prior WBRT and/or SRS at at >28 and >/= 14 days, respectively, prior to starting study drug and the patient must have recovered from the side effects of the therapy
WHO performance status of PT INR Any number of prior HER2-directed and cytotoxic regimens, and the most recent line may be any type of anti-neoplastic therapy

|| Exclusion Criteria:

Patients with untreated brain metastases
Patients with acute or chronic liver, renal disease or pancreatitis
Patients with any peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 2
Patients with a history of mood disorders or ≥ CTCAE grade 3 anxiety
Patient with clinical manifest diabetes mellitus or steroid-induced diabetes mellitus

|| Specific Exclusion Criteria for patients in BM cohorts

Prior treatment with capecitabine
Patient has known dihydropyrimidine dehydrogenase (DPD) deficiency
Patient is currently receiving treatment with EIAED
Other protocol-defined inclusion/exclusion criteria may apply