2018 GU CANCERS SYMPOSIUM: Tivozanib in Combination With Nivolumab in Metastatic RCC

Key Points

  • The combination was generally well tolerated. Treatment-related grade 3/4 adverse events occurred in 44% of patients, the most common of which was hypertension.
  • An objective response rate was observed in 64% of patients (partial responses), and a disease control rate (partial response and stable disease) was observed in 100% of patients.
  • At the time of data collection, 11 of 14 evaluable patients remained on study.

Preliminary results from the phase II portion of the TiNivo study, a phase Ib/II multicenter trial of oral tivozanib in combination with intravenous (IV) nivolumab (Opdivo) for the treatment of metastatic renal cell carcinoma (RCC) were presented by Escudier et al at the 2018 Genitourinary Cancers Symposium (Abstract 618).

Findings

The phase I/II study has enrolled a total of 27 patients. The phase II portion of the study (n = 21) was designed to assess the safety, tolerability, and antitumor activity of the full dose and schedule of oral tivozanib (1.5 mg/d for 21 days followed by a 7-day rest period), as established in the phase I portion of the study (n = 6), in combination with IV nivolumab (240 mg every 2 weeks). The combination was generally well tolerated. Treatment-related grade 3/4 adverse events occurred in 44% of patients, the most common of which was hypertension.

Preliminary efficacy was assessed in 14 patients treated with the full dose and schedule of oral tivozanib in combination with IV nivolumab and enrolled at least 4 months prior to the data cutoff date. Of these, seven had received at least one prior systemic therapy. An objective response rate was observed in 64% of patients (partial responses), and a disease control rate (partial response and stable disease) was observed in 100% of patients. At the time of data collection, 11 of 14 evaluable patients remained on study.

“These preliminary data continue to support the rationale for choosing a high-specificity vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor such as tivozanib in building upon the benefit of immune checkpoint therapy in renal cancer,” said Bernard Escudier, MD, former Chairman of the Genitourinary Oncology Committee, Gustave Roussy, and lead investigator of the study. “Combining VEGF tyrosine kinase inhibitors and immune checkpoint inhibitors has been hampered by toxicity, potentially emerging with the use of other tyrosine kinase inhibitors, while minimal off-target toxicities have been observed with tivozanib in this combination. These results open the possibility for triple-combination therapy using tivozanib, nivolumab and ipilimumab [Yervoy], an immune system activator targeting CTLA-4.”

More About Tivozanib

Tivozanib is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) approved for the treatment of adult patients with advanced RCC in the European Union plus Norway and Iceland. 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. As part of a North American registration plan, tivozanib is currently being studied in the phase III TIVO-3 trial, a randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced RCC.

Tivozanib has been investigated in several tumors types, including renal cell, hepatocellular, colorectal, and breast cancers.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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