However, investigators also find that the combination did not meet the primary end point of increasing progression free survival.
In the TiNivo-2 (NCT04987203) phase 3 clinical trial, investigators compared the combination of nivolumab (Opdivo; Bristol Myers Squibb) and tivozanib (Fotivda; Aveo Oncology), finding that monotherapy with tivozanib demonstrated a clinically meaningful median progression free survival (PFS) following immune checkpoint inhibitor combination (ICI) therapy for advanced metastatic renal cell carcinoma (RCC). However, they also found that the combination did not meet the primary end point of increasing PFS.1
“The PFS and safety of the Fotivda control arm in the second-line following ICI combinations adds to the growing body of evidence of the importance of a highly selective anti-[vascular endothelial growth factor receptor] [tyrosine kinase inhibitor] therapy as an effective, well-tolerated treatment option for relapsed or refractory RCC patients treated with prior ICI combination therapy,” Michael P. Bailey, CEO and president of AVEO Oncology. “While the addition of an ICI to low dose Fotivda did not improve PFS outcomes after prior ICI, we consider the control arm data an important, evidence-based and clinically meaningful contribution to the oncology community treating relapsed or refractory advanced RCC following front-line ICI combinations.”1
In the study, investigators compared the combination of nivolumab and tivozanib with tivozanib as a monotherapy for patients who had advanced RCC and had 1 or 2 lines of prior therapy, including one line of an ICI. The study was an open label, randomized, controlled, multicenter trial to compare the PFS, overall survival (OS), objective response rate (ORR), duration of response (DOR), and safety of both the monotherapy and the combination therapy. Investigators included approximately 190 sites, randomizing treatment 1:1, with the monotherapy receiving 1.34 mg/day of tivozanib or the combination receiving 0.89 mg/day of tivozanib once daily for 3 weeks followed by 1 week off of tivozanib. Nivolumab will be received via infusion as 1 treatment at a specified dose on specified days of each cycle.2
Trial Name: Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma
ClinicalTrials.gov ID: NCT04987203
Sponsor: AVEO Pharmaceuticals Inc
Completion Date (Estimated): July 2026
The primary outcome was PFS for the combination in comparison with the monotherapy. The secondary outcomes included OS, ORR, DOR, and serious and non-serious adverse events.2
Investigators included 343 individuals from November 4, 2021, to June 16, 2023. The median follow-up was 12 months, and there were 171 individuals in the combination group and 172 in the monotherapy group. Investigators reported that the median PFS was 5.7 months with the combination and 7.4 as the monotherapy. For those whose immediate previous therapy was with an ICI (n = 244), there was a median PFS of 7.4 months for the combination and 9.2 months with the monotherapy. For non-ICIs as the most recent therapy, there was a lower median PFS for both groups at 2.7 months.3
There were also 54 serious AEs who received the combination and 64 for those receiving the monotherapy. There was 1 treatment-related death in the monotherapy group.3
