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

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.