A Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma

Exclusion Criteria

• •Has previously been treated with axitinib, AGS-16C3F, or AGS-16M8F
• •Has untreated brain metastasis. In the case of a solitary brain metastasis which has been resected, there must be evidence of a disease-free interval of at least 3 months post-surgery. For brain metastases treated with whole brain or stereotactic radiation therapy, brain imaging must be stable \> 3 months. All subjects previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days prior to C1D1.
• •Has uncontrolled hypertension defined as blood pressure \> 150/90 on medication(s) by 2 blood pressure readings taken at least 1 hour apart.
• •Has gastrointestinal abnormalities including:
• •* inability to take oral medication;
• •* requirement for intravenous alimentation;
• •* prior surgical procedures affecting absorption including total gastric resection;
• •* active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy;
• •* malabsorption syndromes such as celiac disease, cystic fibrosis, inflammatory bowel disease, systemic sclerosis, and carcinoid syndrome
• •Has ocular conditions such as:
• •* Active infection or corneal ulcer
• •* Monocularity
• •* Visual acuity of 20/70 or worse in both eyes
• •* History of corneal transplantation
• •* Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
• •* Uncontrolled glaucoma (topical medications allowed)
• •* Uncontrolled or active ocular problems (e.g., retinopathy, macular edema, active uveitis, wet macular degeneration) requiring surgery, laser treatment, or intravitreal injections
• •* Papilledema or other active optic nerve disorder
• •Has used any investigational drug (including marketed drugs not approved for this indication) ≤ 14 days of C1D1. No time limit applies to the use of marketed drugs approved for this indication provided that the subject has progressed on the treatment and all toxicities attributable to the drug have resolved, returned to baseline or stabilized.
• •Has known sensitivity to any of the ingredients of:
• •* investigational product AGS-16C3F and/or,
• •* Inlyta® (axitinib) and/or,
• •* 1% prednisolone acetate ophthalmic suspension and any other corticosteroids.
• •Is currently using (i.e., within 14-days prior to first dose) drugs that are known strong CYP3A4/5 inhibitors / inducers.
• •Thromboembolic event (e.g., deep vein thrombosis \[DVT\] and pulmonary embolism \[PE\]) ≤ 4 weeks of C1D1.
• •* Subjects who had a thromboembolic event ≤ 4 weeks of C1D1 must be receiving adequate anticoagulation treatment for at least 2 weeks before C1D1 and must continue as clinically indicated post first dose
• •Has history bleeding disorders (e.g., pulmonary hemorrhage, significant hemoptysis, menometrorrhagia not responding to hormonal treatment) ≤ 2 months before C1D1
• •Has active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 6 months of randomization, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, or arrhythmias not controlled by medication.
• •Had major surgery ≤ 4 weeks of C1D1
• •Is pregnant (confirmed by positive serum pregnancy test) or lactating
• •Has active infection requiring treatment with systemic (intravenous or oral) anti-infectives (antibiotic, antifungal, or antiviral agent) ≤ 10 days of C1D1
• •Is unwilling or unable to comply with study requirements
• •Has any medical or psychiatric disorder that compromises the ability of the subject to give written informed consent, and/or comply with the study procedures.