Safety, Tolerability, and Pharmacokinetics of Onartuzumab Combined With Vemurafenib and/or Cobimetinib in Cancer Patients

Inclusion Criteria:

- Adult patients >/= 18 years of age.

- Patients with histologically confirmed, BRAFV600-mutant, unresectable, locally
advanced or metastatic solid malignancies. OR

- Patients with a histologically confirmed, KRAS-mutant, Stage IV colorectal
adenocarcinoma, or KRAS-mutant metastatic non-small-cell lung carcinoma. OR

- Patients with histologically confirmed BRAFV600-mutant unresectable Stage IIIC or
Stage IV metastatic melanoma.

- Valid MET IHC test result.

- Measurable disease per Response Evaluation Criteria in Solid Tumors v1.1

- ECOG performance status of 0 or 1.

- For BRAFV600-mutant cancers:

- Previously untreated for their melanoma or previously treated for their melanoma but
without prior exposure to any HGF, MET, BRAF, or MEK inhibitor therapy

- BRAFV600-mutant solid malignancies other than melanoma for which standard therapy
does not exist has proven to be ineffective or intolerable or is considered
inappropriate.

Patients must not have had prior exposure to HGF, MET, BRAF, or MEK inhibitor therapy.

- For KRAS-mutant cancers:

- mCRC patients must have received therapeutic regimens including oxaliplatin,
irinotecan, 5-FU, and bevacizumab, or determined to be ineligible for these
treatments. Patients must not have had prior exposure to HGF, MET, BRAF, or MEK
inhibitor therapy.

- Metastatic NSCLC patients must have received platinum-based doublet chemotherapy or
determined to be ineligible for this regimen. Patients must not have had prior
exposure to HGF, MET, BRAF, or MEK inhibitor therapy.

- Consent to provide tumor tissue for biomarker analyses.

- Life expectancy >/= 12 weeks.

- Fully recovery from the effects of any major surgery or significant traumatic injury
within 14 days from the first dose of study treatment.

- Adequate hematologic and end organ function, as defined by clinical laboratory
results.

- Use of effective form(s) of contraception as defined by protocol during the course of
this study and for at least 6 months after study drug discontinuation.

Exclusion Criteria:

- Palliative radiotherapy or experimental therapy within 28 days prior to first dose of
study drug treatment.

- Major surgical procedure or significant traumatic injury from 28 days prior to first
dose of study drug treatment until end of study.

- History of another malignancy in the previous 5 years, unless cured by surgery alone
and continuously disease free. Exceptions include appropriately treated cervical
carcinoma in situ, non-melanoma skin carcinoma, Stage I uterine cancer, localized
prostate cancer that has been treated surgically and is presumed cured, or other
malignancies with an expected curative outcome.

- Brain metastasis or spinal cord compression not definitively treated with surgery
and/or radiation, or previously diagnosed and treated central nervous system (CNS)
metastases or spinal cord compression without evidence of clinically stable disease
for more than 14 days.

Note: Patients with treated CNS metastases who are asymptomatic and on a stable dose of
corticosteroids for more than 14 days prior to Cycle 1 Day 1 are eligible.

- For patients given cobimetinib: Evidence of visible retinal pathology that is
considered a risk factor for neurosensory detachment, retinal vein occlusion, or
neovascular macular degeneration, or of conditions that are risk factors for retinal
vein occlusion.

- Current or history of clinically significant cardiac or pulmonary dysfunction.

- Lack of recovery to Grade 1 or better from adverse events due to investigational or
other agents administered more than 28 days prior to enrollment, except for alopecia.

- Current severe, uncontrolled systemic disease.

- Inability or unwillingness to swallow pills.

- History of malabsorption or other condition that would interfere with
gastrointestinal absorption of study drug.

- History of clinically significant liver disease, current alcohol abuse, or known
infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV).

- Severe (Grade 3 and above) active infection at enrollment, or other serious
underlying medical conditions.

- Required medication known to cause edema and/or cardiac failure.

- Active autoimmune disease.

- Uncontrolled ascites requiring weekly, large-volume paracentesis for 3 consecutive
weeks prior to enrollment.