Safety Study of BEZ235 With Everolimus in Subjects With Advanced Solid Tumors

BEZ235 is an agent that was developed to slow down or halt cell growth and proliferation. It
works by inhibiting two pathways that are important for cell growth and replication, one is
called mTOR and the other is called PI3K.

Everolimus is an agent that also targets mTOR thus also slows down cell growth and spread;
in addition, it injures blood vessels that supply cancer cells with nutrition.

The rationale behind combining Everolimus with BEZ235 is to inhibit cell growth and halt
cancer spread by greater degree than either drug alone.

BEZ235 is not approved by the FDA for use in humans outside the context of a clinical trial.

Everolimus is FDA approved for the treatment of renal cell carcinoma (kidney cancer),
subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS), and
Advanced Neuroendocrine Tumors of Pancreatic Origin (PNET).

Inclusion Criteria:

- Histologically or cytologically confirmed advanced solid malignancies that are
metastatic or unresectable, and for which standard/curative measures do not exist by
RECIST 1.1 measureable lesion which is not declining

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

- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

- Adequate bone marrow and organ function as defined by laboratory values

Exclusion Criteria:

- Previous treatment with PI3K inhibitors

- Concurrent malignancy or has a malignancy within 3 years of study enrollment, (with
the exception of adequately treated basal or squamous cell carcinoma or cervical
carcinoma in situ)

- Concurrently using other approved or investigational antineoplastic agent

- Currently receiving anticancer therapies or who have received anticancer therapies
within 4 weeks of the start of study drug (including chemotherapy, radiation therapy,
antibody based therapy, hormonal therapy, etc.)

- Poorly controlled diabetes mellitus (HbA1c > 8 %)

- Chronic treatment with systemic steroids or another immunosuppressive agent

- Active cardiac disease

- Inadequately controlled hypertension (i.e, SBP >180 mmHg or DBP >100mmHg)

- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of BEZ235 (e.g., ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea grade ≥ 2, malabsorption syndrome, or small bowel resection)