50: TiNivo-2: A Phase 3 Study to Compare Tivozanib+Nivolumab to Tivozanib Monotherapy in Patients with Renal Cell Carcinoma (RCC) Who Have Progressed Following ≤2 Lines of Therapy including an Immune Checkpoint Inhibitor (ICI)

Background: Tivozanib, a highly selective and potent VEGFR TKI, has demonstrated efficacy in advanced RCC with minimal off-target toxicities and favorable AE profile. Tivozanib was approved by the FDA for the treatment of patients with RCC who had progressed on ≥2 prior systemic therapies. Tivozanib was combined with nivolumab in a phase 1b/2 trial showing an ORR=56%, DCR=96%, median PFS=18.9 months and tolerable safety profile.

Methods: TiNivo-2 (NCT04987203) is a phase 3, randomized, open-label study to compare tivozanib+nivolumab to tivozanib monotherapy in patients with RCC who have progressed following ≤2 lines of therapy including ICI. Eligibility criteria: ≥18 years, clear cell RCC, ECOG PS 0-1, and disease progression during or following ≥6 weeks of treatment with ICI. Patients will be stratified by IMDC risk category and whether ICI was received in most recent line of treatment. Patients will receive tivozanib 1.34mg orally once daily for 21 days followed by 7 days off as monotherapy, and tivozanib 0.89mg at the same schedule plus nivolumab 480mg intravenously every 4 weeks as combination. Study assessments include CT/MRI of the chest, abdomen, and pelvis every 8 weeks for 2 years and every 12 weeks thereafter until progression. Primary objective is to compare PFS of tivozanib+nivolumab to tivozanib. A sample size of 326 patients, with 191 events will provide ≥80% power to detect a 50% improvement in PFS, 12 months vs. 8 months. Secondary endpoints include OS, ORR, DoR, and safety/tolerability. Exploratory endpoints include QoL (FKSI-DRS and EORTC QLQ C-30) and the pharmacokinetics of tivozanib. TiNivo-2 is actively enrolling and planning to open at 190 sites in the US and EU.