Inclusion Criteria

Key Inclusion Criteria (for Part 3):

- A histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma
which is metastatic (measurable disease).

- Documented KRAS- or BRAF- tumor mutation.

- Previously treated with or unsuitable for treatment with 5-Fluorouracil (5-FU),
oxaliplatin, irinotecan and, if available, bevacizumab.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

- Additional criteria exist.

Key Exclusion Criteria (for Part 3):

- Uncontrolled or symptomatic brain metastases (if the patient has brain metastases and
is on steroids, the steroid dose must have been stable for at least 30 days).

- History of central serous retinopathy, retinopathy visible at baseline that would be
considered a risk factor for central serous retinopathy or retinal vein occlusion.

- Concomitant malignancies or previous malignancies with less than a 2-year disease
free interval at the time of enrollment; patients with adequately resected basal or
squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or stage A low
grade prostate cancer may enroll irrespective of the time of diagnosis.

- Prior treatment with a MEK inhibitor.

- Treatment with prior chemotherapy, anticancer immunotherapy, monoclonal antibodies or
other protein or peptide therapeutics within 21 days of the first dose of study drug.

- Treatment with a small molecule targeted agent or anticancer hormonal therapy within
14 days of the first dose of study drug.

- Treatment with prior radiotherapy within 28 days of initiating study drug (if the
radiation portal covered ≤ 10% of the bone marrow reserve, the patient may be
enrolled irrespective of the end date of radiotherapy).

- Major surgery within 4 weeks or minor surgery within 7 days prior to the first dose
of study drug.

- Known positive serology for the human immunodeficiency virus (HIV), hepatitis C,
and/or active hepatitis B.

- Additional criteria exist.