TiNivo-2 Study of Nivolumab and Tivozanib Fails to Meet Primary End Point in RCC

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Nivolumab (Opdivo) added to 0.89 mg of tivozanib (Fotivda) failed to increase progression-free survival (PFS) in patients with advanced metastatic renal cell carcinoma (RCC) whose tumors had progressed following prior immune checkpoint inhibitor (ICI) treatment, failing to meet the primary end point of the phase 3 TiNivo-2 trial (NCT04987203).¹

However, the control arm of the study evaluating tivozanib alone given at the standard dose of 1.34 mg elicited a clinically meaningful outcome in median PFS in the second line after treatment with an ICI combination. For safety, tivozanib monotherapy was well-tolerated.

These findings build upon the previous ICI data from the phase 3 TIVO-3 (NCT02627963) trial of tivozanib and continue to support the approved use of tivozanib for patients with relapsed/refractory advanced RCC after 2 or more prior systemic therapies.

"The PFS and safety results from the control arm support tivozanib as an effective and well-tolerated treatment option in the second-line following an ICI combination as prior systemic therapy," said Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology, director of the Kidney Cancer Center at Dana-Farber Cancer Institute, Jerome and Nancy Kohlberg Chair and professor of medicine at Harvard Medical School, and lead investigator, in a press release.

The full data from this study will be submitted to an upcoming scientific meeting.

About TiNivo-2

TiNivo-2 is an open-label, randomized, controlled, multicenter, multi-national, parallel-arm trial evaluating the benefit of the addition of nivolumab, a PD-1 checkpoint inhibitor, to low-dose tivozanib compared with tivozanib given at the standard dose in the second-line setting following treatment with ICI combinations or in the third-line setting after prior ICI treatment.²

Approximately 326 patients with RCC who progressed after receiving immunotherapy were randomized to either tivozanib as a single agent or in combination with nivolumab. Enrollment was open across clinical sites in North America, Latin America, and Europe.

Patients histologically or cytologically confirmed RCC with a clear cell component and those with radiographic disease progression during or after at least 6 weeks of treatment with ICI for locally advanced or metastatic RCC with a clear cell component in first-line or second-line treatment were eligible for enrollment if their adverse events from prior therapy had resolved to grade ≤ 1 or baseline. Patients must also have measurable disease per RECIST criteria v1.1, an ECOG performance status of 0 or 1, and be willing to follow all protocol defined contraceptive measures throughout the duration of the study.

The primary end point of the study was PFS. Secondary end points assessed were overall survival, overall response rate, duration of response, and safety.

REFERENCES:

1. AVEO Oncology, an LG chem company, announces phase 3 renal cell carcinoma clinical trial (TiNivo-2) results. News release. AVEO Oncology. July 18, 2024. Accessed July 18, 2024. https://tinyurl.com/unkz8k76

2. Study to compare tivozanib in combination with nivolumab to tivozanib monotherapy in subjects with renal cell carcinoma. ClinicalTrials.gov. Updated April 30, 2024. Accessed July 18, 2024. https://clinicaltrials.gov/study/NCT04987203