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Renal Cell Carcinoma · Post-ICI progression · Reviewed 14 October 2026

TiNivo-2

After one or two prior lines including an ICI, does adding nivolumab to tivozanib improve outcomes compared with tivozanib alone?

Population
343 patients with advanced RCC after 1–2 prior lines including one ICI; 244 had an ICI as their immediate previous therapy.
Experimental arm
Tivozanib 0.89 mg orally daily + nivolumab 480 mg IV every 4 weeks.
Comparator
Tivozanib 1.34 mg orally daily.
Design
Randomized, open-label phase III; primary endpoint PFS by independent radiology review.

Key outcomes

Median PFS — overall
5.7 vs 7.4 months

Tivozanib + nivolumab vs tivozanib; HR 1.10 (95% CI 0.84–1.43), P=0.49.

Median PFS — immediate prior ICI
7.4 vs 9.2 months

Combination vs tivozanib monotherapy among 244 patients whose immediately preceding therapy was an ICI.

Serious adverse events
32% vs 37%

Similar overall serious-event frequency; one treatment-related death occurred in the tivozanib-alone arm.

Interpretation: ICI rechallenge did not help

TiNivo-2 failed its primary endpoint. Adding nivolumab did not improve PFS, including in the subgroup whose immediate prior therapy was an ICI; median PFS was numerically shorter with the combination in both the overall and immediate-prior-ICI populations.

Practice implication: Together with CONTACT-03, TiNivo-2 argues against routine ICI rechallenge after ICI progression in advanced RCC. Tivozanib monotherapy retained activity in the post-ICI setting.

Critical appraisal

The dose of tivozanib differed between arms (0.89 mg with nivolumab versus 1.34 mg as monotherapy), reflecting the combination design and tolerability considerations. The study was open-label, and median follow-up was 12 months. Do not infer equivalence from a non-significant result; rather, the trial did not demonstrate added benefit from nivolumab.

No NNT is calculated because the primary endpoint was negative and the main reported comparison is median PFS/hazard ratio.

Current-practice context

As of 14 October 2026, TiNivo-2 provides phase III evidence that adding PD-1 blockade after prior ICI exposure should not be assumed to restore sensitivity. Select subsequent treatment based on prior VEGFR TKI exposure, available active agents, patient risk and tolerability; use ICI rechallenge preferentially in a clinical trial.

Dated context added 14 October 2026; full guideline audit remains pending.

Sources