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Updated interim results from the phase 2 portion of the TiNivo study, a phase 1b/2 multicenter trial of oral Tivozanib ( Fotivda ) in combination with intravenous Nivolumab ( Opdivo ), an immune checkpoint, or PD-1, inhibitor, for the treatment of advanced or metastatic renal cell carcinoma, were presented at European Society of Medical Oncology ( ESMO ) 2018 Annual Congress.

The phase 1b/2 study has enrolled a total of 28 patients. The phase 2 portion of the study ( n=22 ) was designed to assess the safety, tolerability, and anti-tumor activity of the full dose and schedule of oral Tivozanib ( 1.5 mg/QD for 21 days followed by a 7-day rest period ), as established in the phase 1b portion of the study ( n=6 ), in combination with intravenous Nivolumab ( 240 mg every 2 weeks ).

The combination was generally well tolerated. Treatment-related grade 3-4 adverse events occurred in 60% of patients, the most common of which was hypertension.

Interim efficacy was assessed in all 25 patients treated with the full dose and schedule of Tivozanib in combination with Nivolumab and enrolled at least 4 months prior to the data cutoff date.
Of these, 13 ( 52% ) had received at least one prior systemic therapy.
An objective response rate ( ORR )was observed in 56% of patients ( complete responses plus partial responses ), including 4% of patients ( n=1 ) achieving a complete response, and a disease control rate ( complete response plus partial response plus stable disease ) was observed in 96% of patients.
At the time of data collection 52% ( n=13 ), of patients remained on study.

To date, a total of 72% of patients ( n=18 ) had tumor shrinkage of greater than or equal to 25%, with a majority of patients having disease control for greater than or equal to 48 weeks.

Tivozanib is an oral, once-daily, vascular endothelial growth factor ( VEGF ) tyrosine kinase inhibitor ( TKI ) and approved for the treatment of adult patients with advanced renal cell carcinoma ( RCC ) in the European Union.
It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.
Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models, enabling potentially enhanced activity when used in combination with immune modulating therapy. ( Xagena )

Source: EUSA Pharma, 2018

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