KEY TAKEAWAYS
- Phase III TiNivo-2 study explored the efficacy of tivozanib as a monotherapy and a combination therapy with nivolumab in treating Advanced RCC.
- The study also explored the effect on livability by the drug.
- The study’s primary outcome measure was to determine the Progression Free Survival (PFS) in patients who had progressed after 1 or 2 lines of therapy.
- Compare the PFS of tivozanib in combination with nivolumab to tivozanib.
- Endpoints assess the quality of life (FKSI-DRS and EORTC QLQ C-30) and investigate the pharmacokinetics of tivozanib.
TiNivo-2 Phase III study compared tivozanib and nivolumab and tivozanib monotherapy in RCC patients who have progressed after receiving one to two lines of therapy, including an immune checkpoint inhibitor (ICI).
Advanced renal cell carcinoma (aRCC) has shown single-agent efficacy with tivozanib, a highly potent and selective vascular endothelial growth factor receptor tyrosine kinase inhibitor, low off-target toxicities, and a favorable adverse event profile. Furthermore, the FDA approved tivozanib for treating patients with aRCC who had failed at least two previous systemic therapies.
In the previous phases of the TiNivo study, tivozanib and nivolumab were combined. Results revealed an objective response rate of 56%, a disease control rate of 96%, a median PFS of 18.9 months, and a tolerable safety profile.
The eligibility requirements included ECOG PS 0-1, clear cell RCC, and disease progression during or after at least 6 weeks of ICI therapy for RCC. The IMDC risk category and whether ICI was administered as part of the most recent line of therapy were used to group patients.
On the monotherapy arm, patients received tivozanib 1.34 mg orally once daily for 21 days straight, followed by 7 days off; on the combination arm, patients got tivozanib 0.89 mg at the same timetable in addition to nivolumab 480 mg intravenously every 4 weeks.
Every 8 weeks after Cycle 1 Day 1 for the first two years, and then every 12 weeks after that, until disease progression is verified by independent radiology review, study assessments include CT scans or MRIs of the chest, abdomen, and pelvis (IRR). The main goal was to contrast the progression-free survival (PFS) of tivozanib alone with that of tivozanib in conjunction with nivolumab. An IRR will have at least 80% power to identify a 50% improvement in PFS, measured at 12 months vs. 8 months, with a sample size of 326 patients and 191 events. Secondary outcomes include assessments of overall survival, objective reaction rate, response duration, safety, and tolerability. Exploratory outcomes include measuring livability (FKSI-DRS and EORTC QLQ C-30) and tivozanib pharmacokinetics.
Source:https://kcrs.kidneycan.org/wp-content/uploads/2022/10/Abstracts-Book-KCRS22-website-v3.pdf
https://ascopubs.org/doi/abs/10.1200/JCO.202 2.40.6_suppl.TPS405
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT04987203
Choueiri, T., Albiges, L., McKay, R., Pal, S., Hammers, H., Heng, D., Beckermann, K., Kasturi, V., & Motzer, R. (2022, October 3). TiNivo-2: A Phase 3 Study to Compare Tivozanib Plus Nivolumab to Tivozanib Monotherapy in Patients with RCC Who Have Progressed Following ≤2 Lines of Therapy Including an Immune Checkpoint Inhibitor. KCRS22 Kidney Cancer Research Summit Abstracts, 3, 73–74. https://kcrs.kidneycan.org/wp-content/uploads/2022/10/Abstracts-Book-KCRS22-website-v3.pdf
