57 Final Analysis of the TiNivo-2 Phase 3 Trial: Long-term Outcome of Tivozanib (Tivo) in Patients with Metastatic Renal Cell Carcinoma (mRCC)
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: 4555 Background: TiNivo-2 results showed that immune checkpoint inhibitor (ICI) rechallenge did not offer benefit to patients with mRCC, regardless of treatment sequencing ( Lancet , 2024; 404:1309). However, the data highlights activity for Tivo monotherapy in the post-ICI setting. Long term outcomes of the TiNivo-2 study are reported here. Methods: TiNivo-2 trial design and primary-endpoint results were previously reported: patients with mRCC were randomized to treatment with Tivo 0.89 mg once daily for 21/28 days plus Nivolumab (Nivo) at 480 mg every four weeks (Tivo/Nivo) or Tivo 1.34 mg once daily for 21/28 days. Here, long term progression free survival (PFS), overall survival (OS), and the safety profile are reported at final analysis. Results: At the data cutoff of 17 October 2025, 172 patients were randomized to Tivo (171 treated) and 171 patients were randomized to Tivo/Nivo (168 treated); median (m) follow up was 28.4 mo (95% CI 27.0-29.8) in Tivo versus 27.2 months (mo) (95% CI 26.1-28.5) in Tivo/Nivo. Survival outcomes and hazard ratios (HR) for the ITT population, 2L, and 3L populations are summarized in Table 1. In 2L, mPFS favored Tivo over Tivo/Nivo (9.23 mo [7.29, 11.04] vs 5.95 mo [5.42, 7.95]). Across subgroups, there were no differences in mOS. No new safety signals were observed with prolonged administration; the most common ≥ Grade 3 TEAE was hypertension occurring in 39 (22.8%) and 38 (22.6%) and of patients in the Tivo and Tivo/Nivo groups respectively. Other ≥ Grade 3 TEAEs included diarrhea (2.3% and 3.6%) and palmar-plantar erythrodysaesthesia (0.6% and 1.2%) in the Tivo and Tivo/Nivo groups respectively. Treatment Related SAEs occurred in 15 (8.8%) and 18 (10.7%) of patients in Tivo and Tivo/Nivo groups respectively. Conclusions: This final analysis of patients in the TiNivo-2 study highlights the sustained efficacy Tivo in mRCC with a consistent safety profile. Together, these findings support durable clinical benefit and tolerability of Tivo in the post-ICI treatment setting in RCC, an area of high unmet need (NCT04987203). Clinical trial information: NCT04987203 . Parameter By ITT 2L setting 3L setting Tivo (0.89mg) /Nivo (n=171) Tivo (1.34mg) (n=172) Tivo (0.89mg) /Nivo (n=111) Tivo (1.34mg)(n=105) Tivo (0.89mg) /Nivo (n=60) Tivo (1.34mg)(n=67) mPFS, months (95% CI) 5.72(4.37-7.43) 7.43(5.52-9.23) 5.95(5.42, 7.95) 9.23(7.29, 11.04) 5.45(3.15, 9.56) 5.44(2.10, 7.36) mPFS HR 0.96 (0.76, 1.21) 1.08 (0.80, 1.46) 0.77 (0.52, 1.15) mOS, months (95% CI) 23.85(19.71-NR) 22.93 (18.14-NR) 29.50(21.06, NR) 23.52(18.33, NR) 19.71(10.81, 31.90) 22.70(11.79, NR) mOS HR 0.95 (0.70, 1.28) 0.78 (0.53, 1.16) 1.13 (0.70, 1.81) NR, not reached.
Source: The Oncologist
Authors: Robert Motzer, Bradley McGregor, Laurence Albiges, Javier Molina-Cerrillo, Phillipe Barthelemy, Maria Bourlon, Benjamin Garmezy, Sheik Emambux, Arnab Basu, Raffaele Ratta, Pedro Barata, Jeffrey Yorio, Helen Moon, Alex Chehrazi-Raffle, Roberto Iacovelli, Ralph Hauke, Rana McKay, Kathryn Beckermann, Moshe Ornstein, Toni Choueiri
Institutions: Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, Institut Gustave Roussy, Fondation Gustave Roussy, Hospital Universitario Ramón y Cajal, Hôpitaux Universitaires de Strasbourg, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Sarah Cannon Research Institute, Centre Hospitalier Universitaire de Poitiers, Mayo Clinic, Hôpital Foch, University Hospitals Seidman Cancer Center, Texas Oncology, Kaiser Permanente, City Of Hope National Medical Center, City of Hope, Agostino Gemelli University Polyclinic, Nebraska Cancer Specialists, University of California San Diego, Tennessee Oncology, Cleveland Clinic
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,852
OpenAlex ID: W7162537616
FWCI:
Cites:
Cited by:
Related to: