A Trial of BKM120 (a PI3K Inhibitor) in Patients With Triple Negative Metastatic Breast Cancer

This is a prospective, non-randomized, open-label, multicenter, single-arm exploratory study
of single agent BKM120 in the treatment of metastatic triple negative breast cancer patients.

Patients will first undergo screening, tumor measurement and collection of available tumor
block from the primary tumor and/or a metastatic site. Available tumor block is required in
all patients per inclusion criteria. Analysis of this tumor block will be used for
correlation of predictive markers and clinical response in order to define potential
subpopulation that benefit from BKM120.

Following confirmation of eligibility criteria, subjects will be enrolled. BKM120 will then
be administered in a 100mg dose, orally, once daily, in a continuous schedule. A treatment
cycle is defined as 28 days for the purposes of scheduling procedures and evaluations.

Treatment with BKM120 will continue until disease progression, unacceptable toxicity that
precludes any further treatment, and/or discontinuation of the treatment by investigator or
patient decision.

Inclusion Criteria:

- Pathologically and radiologically confirmed metastatic TNBC (Stage IV disease),
previously documented by histological analysis, which is ER-negative and PR-negative
by IHC and HER2 negative by IHC or FISH/CISH.

- Subjects must have received maximum two prior chemotherapy regimens for metastatic
breast cancer.

- Availability of a representative tumor specimen (primary or metastasis, archival
tissue or fresh biopsy for patients with biopsiable tumor) at baseline.

- At least one measurable lesion by RECIST 1.1

- Age ≥ 18 years at the day of consenting to the study

- ECOG performance status ≤ 2

- Adequate bone marrow and organ function as defined by the following laboratory values:
ANC ≥ 1.0 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9.0 g/dL, INR ≤ 2; serum
potassium between 3.0mmol/L and 5.5 mmol/L; Corrected serum calcium between8.0mg/dL
and 11.5mg/dL (OR between 1.0mmol/L and 1.5mmol/L of Ionized calcium); serum magnesium
between 1.2mg/dL and 3.0 mg/dL; serum creatinine ≤ 1.5 x ULN, ALT and AST within
normal range (or ≤ 3.0 x ULN if liver metastases are present); serum bilirubin within
normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0
x ULN with direct bilirubin within normal range in patients with well documented
Gilbert Syndrome); fasting plasma glucose (FPG) ≤ 140 mg/dL or ≤ 7.8 mmol/L.

Exclusion Criteria:

- Previous treatment with PI3K inhibitors

- Symptomatic CNS metastases

- Patients with controlled and asymptomatic CNS metastases may participate in this
trial. As such, the patient must have completed any prior treatment for CNS metastases
> 28 days (including radiotherapy and/or surgery) prior to enrollment in this study.
Patients with previously treated brain metastases, who are on a stable low dose
corticosteroids treatment are eligible

- Concurrent malignancy or malignancy within 3 years of study enrollment (with the
exception of adequately treated basal or squamous cell carcinoma or non-melanomatous
skin cancer). An exception to this rule are those patients with documented germline
mutations in BRCA1 or 2, who may have previous history of cancer

- Any of the following mood disorders as judged by the Investigator or a Psychiatrist,
or meets the cut-off score of ≥ 10 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood
scale, respectively, or selects a positive response of '1, 2, or 3' to question number
9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the
total score of the PHQ-9)

1. Patients with a history or active episodes of major depression, bipolar disorder
(I or II), obsessive-compulsive disorder, schizophrenia, history of suicide
attempts or suicidal thoughts (eg. Risk of hurting or harming others) or patients
with severe personality disorders (as defined by the DSM-IV) are not eligible.
Note: For patients who are treated with psychotropic drugs at baseline, the dose
and schedule shall not be changed during the 6 weeks prior to initiation of
treatment with the study drug.

2. ≥ CTCAE v 4.0 grade 3 anxiety

- Patients on concurrent use of other approved or investigational antineoplastic and /
or chemotherapy or any continuous or intermittent treatment with therapeutic agents of
low molecular weight (excluding monoclonal antibodies) in ≤ 21 days prior to
enrollment in this study or who have not recovered from the effects such therapy will
not be eligible.

- Radiotherapy ≤ 28 days prior to enrollment in this study or failure to recover from
side effects of such therapy at the time of initiation of screening procedures.

- Major surgery within 28 days prior to starting study drug or has not recovered from
major side effects of the surgery

- Poorly controlled diabetes mellitus (HbA1c > 8%)

- Active cardiac disease including any of the following:

1. Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated
acquisition (MUGA) scan or echocardiogram (ECHO)Note: ECHO/MUGA is only required
at baseline if patient has a history of abnormal cardiac test results

2. QTc > 480 msec on screening ECG (using the QTcF formula

3. Angina pectoris that requires the use of anti-anginal medication

4. Ventricular arrhythmias except for benign premature ventricular contractions

5. Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication

6. Conduction abnormality requiring a pacemaker

7. Valvular disease with documented compromise in cardiac function

8. Symptomatic pericarditis

- History of cardiac dysfunction including any of the following;

1. Myocardial infarction within the last 6 months, documented by persistent elevated
cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF
function

2. History of documented congestive heart failure (New York Heart Association
functional classification III-IV)

3. Documented cardiomyopathy

- Treatment with QT prolonging medication known to have a risk to induce Torsades de
Pointes, and the treatment cannot be discontinued or switched to a different
medication prior to starting study drug

- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of BKM120 (e.g., uncontrolled nausea, vomiting, diarrhea,
malabsorption syndrome, or small bowel resection)

- Chronic treatment with steroids or another immunosuppressive agent. Note: Topical
applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye
drops or local injections (e.g., intra-articular) are allowed. Patients with
previously treated brain metastases, who are on a stable low dose corticosteroids
treatment (e.g., dexamethasone 2 mg/day, prednisone 10 mg/day) for at least 14 days
before start of study treatment, are eligible

- Other concurrent severe and/or uncontrolled medical condition that would, in the
investigator's judgment contraindicate her participation in the clinical study (e.g.,
chronic pancreatitis, active chronic hepatitis etc.)

- History of non-compliance to medical regimen

- Current treatment with drugs known to be moderate and strong inhibitors or inducers of
isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different
medication prior to starting study drug

- Known history of HIV (testing not mandatory) infection

- Pregnant or nursing (lactating) woman

- Woman of child-bearing potential unwilling to observe total sexual abstinence or to
use a double barrier method for birth control throughout the trial. Reliable
contraception should be maintained throughout the study and for 6 months after study
drug discontinuation