A Phase I/IB Trial of MEK162 in Combination With Erlotinib in Non-Small Cell Lung Cancer (NSCLC) Harboring KRAS or EGFR Mutation
- Eligible patients will have a histologic or cytologic diagnosis of NSCLC of the
advanced stage (IV), with no known curative treatment options.
- Have a biopsy proven KRAS or EGFR mutation confirmed in a Clinical Laboratory
Improvement Amendments (CLIA)certified lab (only required in the Phase IB expansion
- Have received at least one previous line of therapy except for patients with a CLIA
confirmed EGFR mutation and who are treatment naïve.
- Patients with a CLIA confirmed EGFR mutation may enroll in either the Phase I or
Phase IB arms of the study because both treatment arms include erlotinib in the first
line, which is the standard of care for treated of stage IV EGFR mutated
- Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1
- Patients will have received no more than 4 lines of previous chemotherapy in the
Phase I arm only.
- Patients will have received no more than 2 lines of previous chemotherapy in the
Phase IB arm only.
- 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 28 days prior to enrolling in the study.
- Have discontinued all previous biologic therapies and recovered from side effects due
to biologic treatment for more than 28 days prior to study enrollment.
- Have discontinued all previous external beam radiation therapy and recovered from
side effects due to radiation therapy for more than 28 days prior to study
- Erlotinib naïve (required for both Phase I and IB).
- Have archival tissue available or be willing to undergo a repeat biopsy.
- 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
- 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 (except erlotinib
per this study protocol) or investigational agents
- Gastrointestinal disease that precludes absorption
- History or current evidence of central serous retinopathy (CSR) or retinal vein
- 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 28 days prior to study enrollment; radiation
therapy less than 28 days prior to study enrollment; biologic therapy less than 28
days prior to study enrollment
- 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 28 days prior
to study enrollment; Received previous radiation therapy and has not recovered from
side effects for more than 28 days prior to study enrollment; Received previous
biologic therapy and has not recovered from side effects for more than 28 days prior
to study enrollment
- 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
- Women who are pregnant or nursing
- WOCBP, UNLESS using 2 approved birth control methods
- Unwilling or unable to comply with the protocol
- Known positive serology for HIV, active Hepatitis B, and/or active Hepatitis C
- History of Gilbert's syndrome
- Neuromuscular disorders that are associated with elevated creatine 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