On March 10, 2021, the U.S. Food and Drug Administration (FDA) approved tivozanib (Fotivda®), a kinase inhibitor, for adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FDA approved the application three weeks ahead of its goal date.

FDA Approves Tivozanib for Relapsed or Refractory Advanced Renal Cell Carcinoma

Efficacy was evaluated in a randomized, open-label, multicenter trial (TIVO-3; NCT02627963) of tivozanib or sorafenib in patients with relapsed or refractory advanced RCC who received two or three prior systemic treatments, including at least one vascular endothelial growth factor receptor kinase inhibitor other than sorafenib or tivozanib. Patients were randomized 1:1 to receive either tivozanib 1.34 mg orally once daily for 21 consecutive days every 28 days (n = 175) or sorafenib 400 mg orally twice a day continuously (n = 175) until they experienced disease progression or unacceptable toxicity.

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 (95% CI = 4.8, 7.3) in the tivozanib arm compared to 3.9 months (95% CI = 3.7, 5.6) for those treated with sorafenib (hazard ratio = 0.73; 95% CI = 0.56, 0.95; p = 0.016). Median OS was 16.4 (95% CI = 13.4, 21.9) and 19.2 months (95% CI = 14.9, 24.2) for the tivozanib and sorafenib arms, respectively (hazard ratio = 0.97; 95% CI = 0.75, 1.24). ORR was 18% (95% CI = 12%, 24%) for the tivozanib arm and 8% (95% CI = 4%, 13%) for the sorafenib arm.

The most common adverse reactions (≥ 20%) were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis. The most common grade 3 or 4 laboratory abnormalities (≥ 5%) were decreased sodium, increased lipase, and decreased phosphate.

The recommended tivozanib dose is 1.34 mg once daily, with or without food, for 21 consecutive days every 28 days until patients experience disease progression or unacceptable toxicity.

View full prescribing information for tivozanib.

Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine or device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.