Dr Chehrazi-Raffle on the TiNivo-2 Study of Tivozanib With/Without Nivolumab in mRCC

“Of the 343 patients in the phase 3 trial, there were a substantial amount that received the medications in unconventional settings, [including] post-adjuvant [therapy] or in a clinical trial that preceded treatment.”

Alexander Chehrazi-Raffle, MD, an assistant professor in the Department of Medical Oncology & Therapeutics Research at City of Hope, discussed the clinical rationale for a subgroup analysis of the phase 3 TiNivo-2 study (NCT04987203) of tivozanib (Fotivda) with or without nivolumab (Opdivo) in patients with metastatic renal cell carcinoma (mRCC).

TiNivo-2 was a global, randomized study that compared tivozanib plus nivolumab vs tivozanib monotherapy in patients with mRCC following treatment with immunotherapy, Chehrazi-Raffle began. The study enrolled a total of 343 patients, he added. Primary data from TiNivo-2 revealed that the study did not meet its primary end point of progression-free survival (PFS), he noted.

However, there were a significant number of patients who received the combination of tivozanib and nivolumab in unconventional settings, including after adjuvant therapy or following participation in a clinical trial, Chehrazi-Raffle said. During the 2025 ASCO Annual Meeting, Chehrazi-Raffle presented data from a subgroup analysis of TiNivo-2 that included patients who received tivozanib plus nivolumab following nivolumab plus ipilimumab (Yervoy) or after treatment with a VEGF inhibitor in combination with an immune checkpoint inhibitor (ICI).

Findings from the subgroup analysis revealed that patients who received the combination following treatment with a VEGF TKI plus an ICI (n = 42) achieved a median PFS of 3.91 months (95% CI, 2.14-6.74) compared with 7.43 months (95% CI, 3.65-9.33) among patients who received tivozanib monotherapy in this setting (n = 41; HR, 1.20; 95% CI, 0.71-2.02; log-rank P = .5139). Patients who received the combination following frontline nivolumab plus ipilimumab (n = 33) experienced a median PFS of 9.33 months (95% CI, 7.26-15.34) compared with 9.20 months (95% CI, 4.50-not reached) in the monotherapy arm (n = 37; HR, 1.05; 95% CI, 0.51-1.95; log-rank P = .8719). The study authors concluded that the results of the subgroup analysis were consistent with the parent trial in that there was no benefit with the addition of nivolumab to tivozanib in this context.