KEY TAKEAWAYS
- The TiNivo-2 phase 3 trial aimed to evaluate whether tivozanib + nivolumab improves outcomes vs. tivozanib alone in patients with RCC after ICI.
- The primary endpoint was PFS.
- The study concluded that ICI rechallenge didn’t improve outcomes, supporting tivozanib monotherapy as second-line treatment.
Tivozanib, a selective vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), has shown efficacy as a single agent and in combination with ICIs in renal cell carcinoma (RCC) treatment.
Toni K. Choueiri and the team designed the TiNivo-2 study, that aimed to compare the combination of PD-1 inhibitor nivolumab and tivozanib vs. tivozanib monotherapy after tumor progression on prior ICI therapy.
This phase III clinical trial enrolled patients with advanced clear-cell RCC who had received 1-2 prior lines of therapy, including an ICI. Patients were randomized to receive either tivozanib (0.89 mg) plus nivolumab or tivozanib (1.34 mg) alone.
The primary endpoint was progression free survival (PFS) assessed by independent radiology review (IRR). Secondary endpoints included overall survival (OS), investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), and safety/tolerability.
About 343 patients were randomized to the tivozanib-nivolumab (n=171) or tivozanib (n=172) arm. The study did not meet its primary endpoint, as the median IRR-assessed PFS was 5.7 months for tivozanib-nivolumab and 7.4 months for tivozanib (HR 1.10, 95% CI 0.82-1.43). Grade 3 or higher adverse events (AEs) were observed in 205 (60%) patients, with hypertension being the most frequent (22% in both arms).
The addition of nivolumab to tivozanib did not improve clinical outcomes in patients with advanced RCC who had progressed on previous ICI combination therapy. The findings suggested that sequential ICI use in this setting should be avoided outside of clinical trials.
Based on these results, tivozanib monotherapy at a dose of 1.34 mg daily is suggested as a potential second-line treatment option for these patients.
The trial was sponsored by AVEO Pharmaceuticals, Inc.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/14
Clinical Trial: https://clinicaltrials.gov/study/NCT04987203
Choueiri TK, Motzer RJ, Beckermann K, et al. (2024). “Tivozanib–nivolumab vs tivozanib monotherapy in patients with renal cell carcinoma (RCC) following 1 or 2 prior therapies including an immune checkpoint inhibitor (ICI): Results of the phase III TiNivo-2 study.” Presented at: ESMO Congress 2024; 2024; LBA73.
