FOTIVDA (tivozanib), an oral next-generation VEGFR TKI, has shown efficacy as a single agent following prior VEGFR TKI and ICI therapies, and in combination with ICIs. It was FDA-approved in March 2021 for relapsed/refractory advanced RCC after two or more prior systemic treatments, based on the TIVO-3 trial. 

The Phase III TiNivo-2 trial evaluated the combination of tivozanib and the PD-1 inhibitor nivolumab versus tivozanib alone in patients with tumor progression after previous ICI-based therapy. The primary endpoint was PFS and the key secondary endpoint was OS.

Results presented at the ESMO 2024 conference, showed that the study did not achieve its primary endpoint, with a median IRR-assessed PFS of 5.7 months for the tivozanib–nivolumab combination and 7.4 months for tivozanib alone. 

Efficacy data is summarized in the table below: 

In terms of safety, Grade 3 or higher adverse events occurred in 60% of patients, with hypertension being the most common (22% in both arms). Deaths due to adverse events were reported in 4.2% of the tivozanib–nivolumab group and 2.9% of the tivozanib group, with one treatment-related death in the tivozanib arm.

KOL insights

“ICI + TIVOZANIB in IO pretreated M1 renal cancer showed retreatment with IO makes absolutely no difference. We need to stop retreating with IO. These data apply in the post adjuvant setting too without data”- Professor of Urology Cancer, University of London

Conclusion 

Renal cell carcinoma is the most common type of kidney cancer accounting for around 90% of all kidney cancers. The RCC treatment landscape has become increasingly competitive, with TKIs, immunotherapy, and combination regimens becoming the cornerstone of treatment. 

Data from the Phase III TiNivo-2 trial highlighted at the ESMO 2024 showed that the combination of tivozanib–nivolumab failed to meet the primary endpoint. The lack of improved clinical outcomes with ICI combination suggests that sequential ICIs should be avoided outside of clinical trials for advanced RCC. However, this data adds to the growing body of evidence of using FOTIVDA monotherapy at 1.34 mg daily as a preferred second-line treatment option for patients who have progressed after prior ICI combination therapy.

AVEO’s Phase III disappointment follows a similar failure by BMS, which in January 2024 reported that OPDIVO did not significantly improve disease-free survival in localized RCC patients in the Phase III CheckMate-914 trial. In contrast, Merck is making progress in RCC treatment, with the FDA approval of its HIF-2α inhibitor WELIREG in December 2023 for patients with advanced disease who had previously been treated with a PD-1 blocker and a VEGF inhibitor. 

 

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Renal Cell Carcinoma - Market Insight, Epidemiology and Market Forecast - 2032.