Dr Beckermann on the Role of Tivozanib in Advanced Clear Cell RCC

“[The phase 3 TiNivo-2] study was extremely informative, though it was a negative study, it actually proved—and should be emphasized—that we should not continue IO after progression on frontline IO.”

Kathryn E. Beckermann, MD, PhD, assistant professor, Department of Medicine, Division of Hematology and Oncology, Vanderbilt School of Medicine, details the role of tivozanib (Fotivda) in the second- and third-line setting following an immune checkpoint inhibitor in patients with locally advanced or metastatic clear cell renal cell carcinoma (ccRCC).

The phase 3 TiNivo-2 study (NCT04987203), which investigated tivozanib plus nivolumab (Opdivo) vs tivozanib alone in locally advanced or metastatic ccRCC, was a negative study after missing its primary end point of progression-free survival (PFS), Beckermann begins. However, the study provided valuable insight on rechallenging with an immune checkpoint inhibitor (ICI) after disease progression on a frontline ICI-based regimen, she emphasizes.

PRO data from the study recently presented at the 2025 Genitourinary Cancers Symposium showed that treatment with tivozanib/nivolumab vs tivozanib monotherapy resulted in comparable outcomes. Patients on the study were given the Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index-Disease-Related Symptoms (FKSI-DRS) and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaires. Notably, patients in the intent-to-treat (ITT) populations from the combination and monotherapy arms, respectively, demonstrated mean FKSI-DRS scores of 28.8 vs 29.3 at baseline; mean EORTC QLQ-C30 scores at baseline were 63.4 vs 66.2 in the respective arms.

Of note, patients in the study were treated with tivozanib either in the second- or third-line setting, Beckermann explains. In patients from the ITT population treated with tivozanib monotherapy, the median PFS was 7.3 months in the second line and 4.8 months in the third line, she adds. Within the lower-dose tivozanib plus nivolumab arm, patients treated in the second line had a median PFS of 9.2 months and 5.5 months in the third line, Beckermann concludes.