FDA Accepts NDA for Tivozanib in Relapsed/Refractory Renal Cell Carcinoma


"The acceptance of our NDA filing marks yet another important milestone for AVEO, as we pursue our goal of providing RCC patients whose disease has relapsed or become refractory to multiple lines of therapy with a meaningful new treatment option."

A New Drug Application (NDA) for tivozanib (Fotivda) has been accepted by the FDA. The NDA is seeking FDA approval for the treatment of patients with relapsed or refractory renal cell carcinoma (RCC). The application will undergo standard FDA review and was given a Prescription Drug Use Fee Act action date of March 31, 2021. The Oncologic Drug Advisory Committee (ODAC) will not be involved with the review of the NDA for tivozanib.1

“The acceptance of our NDA filing marks yet another important milestone for AVEO, as we pursue our goal of providing RCC patients whose disease has relapsed or become refractory to multiple lines of therapy with a meaningful new treatment option,” said Michael Bailey, president, and chief executive officer, AVEO. “We look forward to working closely with the FDA over the coming months during their review of our application. In parallel, we continue to focus on commercial-readiness to ensure we are well-positioned to support the potential launch of tivozanib, subject to approval.”

The NDA was accepted based on data from the phase 2 TVIO-3 clinical trial, for which data were presented during the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program. In the study, tivozanib demonstrated superiority over sorafenib (Nexavar) as treatment of refractory metastatic RCC.

With a median follow-up of 38 months in the tivozanib arm and 40 months in the sorafenib arm, a final overall survival (OS) hazard ratio of 0.97 was observed (95% CI, 0.75-1.24; P =.78). The median OS in the tivozanib arm was 16.4 months (95% CI, 13.4-22.2) and 19.2 months in the sorafenib arm (95% CI, 15.0-24.2). In a subgroup of patients who received previous checkpoint inhibitor and VEGF inhibitor therapy, the HR was 0.55 and was 0.57 for those who received 2 prior checkpoint or VEGF inhibitors. As reported prior to the 2020 ASCO meeting, the median progression-free survival for tivozanib was 5.6 months versus 3.9 months for sorafenib (HR, 0.73; 95% CI, 0.56-0.94; P =.016).2

Tivozanib also led to an objective response rate of 34% compared with 24% for sorafenib. Responses were partial responses, which occurred in 80% of patients in the tivozanib arm versus only 8% of those in the sorafenib arm.

The safety profile observed with tivozanib in TIVO-3 was favorable with treatment-related adverse events (AEs) occurring in 84% of patients in the tivozanib group and 94% of patients who received sorafenib. Eleven percent of patients who were treated with tivozanib experienced serious treatment-related AEs compared with 10% of the sorafenib group.

In terms of grade 3 or 4 AEs, the majority of patients experienced hypertension (38%), diarrhea (33%), fatigue (29%), and decreased appetite (27%). Dose reductions were necessary for 48% of patients in the tivozanib arm versus 63% in the sorafenib arm (P =.0164). Eight percent of patients who received tivozanib discontinued treatment compared with 15% of those who received sorafenib.

TIVO-3 is a controlled, multicenter, open-label, phase III trial of 350 patients with highly refractory metastatic RCC who had failed ≥2 prior regimens, including VEGF tyrosine kinase inhibitor (TKI) treatment. Patients in the study were randomized 1:1 to receive either oral tivozanib or sorafenib. No crossover between arms was allowed.

In addition to TIVO-3, the basis for the potential approval of tivozanib for the treatment of r/r RCC also comes 3 other clinical trials. First, the phase 3 TIVO-1 study (NCT01030783) evaluated frontline tivozanib compared to sorafenib in this patient population, then 902, a phase 2, open-label study (NCT01076010) explored tivozanib crossover for patients who progressed on sorafenib in the TIVO-1 study. The final study being considered in the NDA review for tivozanib in the phase 2 study, 201 (NCT00502307), which assessed frontline tivozanib in RCC with a placebo control. Together, these clinical trials provide data from over 1,000 patients.

Tivozanib is an oral next-generation VEGFR TKI used to treat adult patients with advanced RCC. The drug has prior indications in the European Union United Kingdom, Norway, and New Zealand.


1. AVEO Oncology announces FDA acceptance for filing of a new drug application for tivozanib as a treatment of relapsed or refractory renal cell carcinoma. News release. AVEO Oncology. June 1, 2020. Accessed June 1, 2020. https://bit.ly/3gCdbUi.

2. Pal SK, Escudier B, Atkins MB, et al. TIVO-3: Final OS analysis of a phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC). Presented at: 2020 ASCO Virtual Program; May 27, 2020. Abstract 5062.

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