Adding nivolumab to low-dose tivozanib does not improve PFS in renal cell carcinoma

The phase 3 TiNivo-2 trial (NCT04987203) failed to meet its primary end point, demonstrating that the addition of nivolumab (Opdivo) to low dose (0.89 mg) tivozanib (Fotivda) did not improve progression-free survival (PFS) compared with standard dose tivozanib alone in patients with advanced metastatic renal cell carcinoma (RCC) whose tumors progressed following prior treatment with an immune checkpoint inhibitor (ICI).¹

Data from the trial are expected to be presented at an upcoming medical meeting.

These results are consistent with data from other recent phase 3 trials in a similar patient population. According to a news release from AVEO, the TiNivo-2 trial is the “second phase 3 clinical trial to suggest that there is no clinical benefit derived from rechallenging RCC patients with immunotherapy after receiving ICI beyond progression on previous ICIs.”¹

However, data from the trial reinforce the efficacy of tivozanib monotherapy, a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), in this patient population. Patients in the control arm who received a standard dose (1.34 mg) of tivozanib demonstrated a clinically meaningful outcome in median PFS.

"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 principal investigator Toni Choueiri, MD, in a news release on the findings.¹ Choueiri is the director of the Lank Center for Genitourinary Oncology, the director of the Kidney Cancer Center at Dana-Farber Cancer Institute, and the Jerome and Nancy Kohlberg Chair and professor of medicine at Harvard Medical School in Boston, Massachusetts.

In total, the phase 3 TiNivo-2 trial enrolled 343 adult patients with advanced RCC who had received 1 or 2 prior lines of therapy, one of which was an ICI.² Patients were enrolled across clinical trial sites in North America, Latin America, and Europe.

To be eligible for enrollment, patients needed to have histologically or cytologically confirmed RCC with a clear cell component, measurable disease per RECISTv1.1, and an ECOG performance score of 0 or 1. Additionally, patients needed to have recovered from adverse events of prior therapies to grade 1 or lower or to baseline.²

Those included in the trial were randomly assigned to receive nivolumab every 4 weeks in combination with low dose (0.89 mg) tivozanib once daily for 3 weeks followed by 1 week off or to standard dose (1.34 mg) tivozanib monotherapy once daily for 3 weeks followed by 1 week off. The primary end point for the trial was PFS. Secondary end points included overall survival, overall response rate, duration of response, and safety.

According to AVEO, detailed results from the trial are expected to be presented at an upcoming scientific meeting.

"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-VEGFR TKI therapy as an effective, well-tolerated treatment option for relapsed or refractory RCC patients treated with prior ICI combination therapy," said Michael P. Bailey, CEO and president of AVEO Oncology, in the news release.¹ "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."

References

1. AVEO Oncology, an LG Chem company, announces phase 3 renal cell carcinoma clinical trial (TiNivo-2) results. News release. AVEO, an LG Chem Company. July 18, 2024. Accessed July 19, 2024. https://www.aveooncology.com/aveo-oncology-an-lg-chem-company-announces-phase-3-renal-cell-carcinoma-clinical-trial-tinivo-2-results/

2. Study to compare tivozanib in combination with nivolumab to tivozanib monotherapy in subjects with renal cell carcinoma. ClinicalTrial.gov. Last updated April 30, 2024. Accessed July 19, 2024. https://clinicaltrials.gov/study/NCT04987203