Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma

Prior treatment

• Subjects who received: a. A single agent tyrosine kinase inhibitor (TKI) in the first line setting followed by a single agent immune checkpoint inhibitor (ICI) in the second line setting; b. More than 2 prior lines of therapy in the advanced or metastatic setting.
• History of life-threatening toxicity related to prior immune therapy.
• Active autoimmune disease as well as those that required discontinuation of prior immuno-oncological (IO) therapy due to immune mediated AEs.
• More than 1 prior line of therapy with a checkpoint inhibitor in the metastatic setting.

Other illness

• Uncontrolled hypertension.
• History of clinically significant interstitial lung disease or current non-infectious pneumonitis.

Lab values

• Subjects on immune suppressive therapy for organ transplant or subjects with a history of genetic or acquired immune suppression disease such as human immunodeficiency virus (HIV) \[Patients with HIV who have CD4+ T-cell counts \>350 cells/µL, without a history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections, and are on established antiretroviral therapy which does not include a cytochrome P450 (CYP)3A4 inducer, for at least 4 weeks and have an HIV viral load less than 400 copies/mL, are eligible\].

• Radiographic disease progression during or following at least 6 weeks of treatment with ICI for locally advanced or metastatic RCC with a clear cell component either in first- or second-line treatment.
• Subjects must have recovered from the adverse events of prior therapy to grade ≤ 1 or baseline.
• Histologically or cytologically confirmed RCC with a clear cell component.
• Measurable disease per RECIST criteria Version 1.1.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• All participants must follow protocol defined contraceptive measures.