General Information

Fotivda (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI).

Fotivda is specifically indicated for the treatment of adults with relapsed or refractory advanced renal cell carcinoma (RCC) who have received two or more prior systemic therapies.

Fotivda is supplied as a capsule for oral administration. The recommended dose is 1.34 mg taken orally once daily for 21 days on treatment followed by 7 days off treatment for a 28-day cycle. Continue treatment until disease progression or until unacceptable toxicity occurs.

Fotivda can be taken with or without food. Swallow the Fotivda capsule whole with a glass of water. Do not open the capsule. If a dose is missed, the next dose should be taken at the next scheduled time. Do not take two doses at the same time.

Clinical Trials

The FDA approval of Fotivda was based on TIVO-3, a randomized (1:1), open label, multicenter trial comparing Fotivda to sorafenib in relapsed or refractory advanced RCC following two or more prior systemic therapies. Patients (n=350) enrolled in the TIVO-3 study were randomized 1:1 to receive either Fotivda or sorafenib. The main efficacy outcome measure was progression-free survival (PFS), assessed by a blinded independent radiology review committee. Other efficacy endpoints were overall survival (OS) and objective response rate (ORR). Median PFS was 5.6 months in the Fotivda arm (n=175) compared with 3.9 months for those treated with sorafenib. Median OS was 16.4 and 19.2 months for the Fotivda and sorafenib arms, respectively. The ORR was 18% for the Fotivda arm and 8% for the sorafenib arm.

Mechanism of Action

Fotivda (tivozanib) is a tyrosine kinase inhibitor. In vitro cellular kinase assays demonstrated that tivozanib inhibits phosphorylation of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2 and VEGFR-3 and inhibits other kinases including c-kit and PDGFR β at clinically relevant concentrations. In tumor xenograft models in mice and rats, tivozanib inhibited angiogenesis, vascular permeability, and tumor growth of various tumor cell types including human renal cell carcinoma.