A Phase I/IB Trial of MEK162 in Combination With Erlotinib in NSCLC Harboring KRAS or EGFR Mutation

Inclusion Criteria:

- Eligible patients will have a histologic or cytologic diagnosis of NSCLC of the
advanced stage (IV), with no known curative treatment options.

- Have a tissue or blood proven KRAS or EGFR mutation confirmed in a Clinical Laboratory
Improvement Amendments (CLIA)certified lab (only required in the Phase IB expansion
cohort).

- For Phase I/Ib enrollment, Patients with a CLIA confirmed EGFR mutation may be
treatment naïve. All other patients must have received at least one previous line of
therapy. There will be no limits to prior lines of treatment for the Phase 1 portion.

- Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1

- There will be no limits to prior lines of treatment.

- At least one measurable site of disease (as defined by Response Evaluation Criteria in
Solid Tumors), or other disease specific response assessment criteria, as appropriate
(RECIST 1.1).

- Have discontinued all previous systemic therapies and recovered from side effects due
to systemic treatment for more than 14 days prior to starting on treatment.

- Have discontinued all previous biologic therapies and recovered from side effects due
to biologic treatment for more than 14 days prior to starting on treatment.

- Have discontinued all previous external beam radiation therapy and recovered from side
effects due to radiation therapy for more than 14 days prior to starting on treatment.

- Have archival tissue sample (if available) or be willing to undergo a repeat biopsy
(if feasible).

- Negative serum pregnancy test within 72 hours prior to the first study dose in all
women of childbearing potential (WOCBP).

- Adequate organ function and lab parameters

- Prior to any screening or invasive procedure, written informed consent must be
obtained.

Exclusion Criteria:

- Does not have adequate cardiac function

- Patients with documented central nervous system or leptomeningeal metastasis (brain
metastasis) at time of study entry. Patients with prior brain metastasis may be
considered if they have completed their treatment for brain metastasis, no longer
require corticosteroids, and are asymptomatic.

- Any other serious uncontrolled medical disorder or active infection that would impair
the patient's ability to receive study treatment

- Prior use of MEK162 or concurrent use of other approved anticancer or investigational
agents. Patients treated with prior EGFR TKI therapy (including erlotinib) are allowed
to enroll.

- Gastrointestinal disease that precludes absorption

- History or current evidence of central serous retinopathy (CSR) or retinal vein
occlusion (RVO)

- Any ophthalmopathy visible at screening that would be considered a risk factor for CSR
or RVO by the ophthalmologist

- History of another malignancy within 2 years, except cured basal cell carcinoma of the
skin or excised carcinoma in situ of the cervix

- Patients who have received prior anti-cancer treatment within the following time
frames: systemic therapies less than 14 days prior to starting on treatment; radiation
therapy less than 14 days prior to starting on treatment; biologic therapy less than
14 days prior to starting on treatment.

- Patients who have not recovered from side effects of prior anti-cancer treatment to
less than or equal to grade 1 toxicity according to Common Toxicity Criteria for
Adverse Effects (CTCAE) v.4 within the following time frames: Received previous
systemic therapy and has not recovered from side effects for more than 14 days prior
to starting on treatment; Received previous radiation therapy and has not recovered
from side effects for more than 14 days prior to starting on treatment; Received
previous biologic therapy and has not recovered from side effects for more than 14
days prior to starting on treatment

- Have undergone major surgery < 4 weeks of initiation of study medication or who have
not recovered from side effects of such procedure

- Patients with concurrent uncontrolled medical conditions that may interfere with their
participation in the study or potentially affect the interpretation of the study data

- Women who are pregnant or nursing

- Women of child-bearing potential (WOCBP) and males who have not been sterilized by
vasectomy or other means with partners who are WOCBP, UNLESS the women are using two
birth control methods. The two methods can be a double barrier method or a barrier
method plus a hormonal method.

- Unwilling or unable to comply with the protocol

- Known positive serology for HIV, active Hepatitis B, and/or active Hepatitis C
infection

- History of Gilbert's syndrome

- Neuromuscular disorders that are associated with elevated creatinine kinase (CK)

- Patients who are planning on embarking on a new strenuous exercise regimen after first
dose of study treatment. Muscular activities, such as strenuous exercise, that can
result in significant increases in plasma CK levels should be avoided while on MEK162
treatment.

- Previous treatment with any substrate of CYP2B6 enzyme < 14 days prior to initiation
of investigational products