On October 22, 2018 AVEO Oncology (NASDAQ:AVEO) and EUSA Pharma reported the presentation of updated interim results from the Phase 2 portion of the TiNivo study, a Phase 1b/2 multicenter trial of oral (PO) tivozanib (FOTIVDA) in combination with intravenous (IV) nivolumab (OPDIVO, Bristol-Myers Squibb), an immune checkpoint, or PD-1, inhibitor, for the treatment of advanced or metastatic renal cell carcinoma (Press release, AVEO, OCT 22, 2018, View Source [SID1234530044]). The results were presented today at European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Annual Congress, in a poster presentation titled "TiNivo: Tivozanib Combined with Nivolumab: Safety and Efficacy in Patients with Metastatic Renal Cell Carcinoma (mRCC)" (Presentation 878P). A copy of the presentation is available at www.aveooncology.com or further information can be obtained via EUSA Pharma Medical Information.
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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 PO 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 IV 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 PO tivozanib in combination with IV 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 was observed in 56% of patients (complete responses + partial responses), including 4% of patients (n=1) achieving a complete response, and a disease control rate (complete response + partial response + 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 ≥25%, with a majority of patients having disease control for ≥48 weeks.
"With high and durable tumor shrinkage rates for the combination of tivozanib and nivolumab, including a complete response, coupled with a favorable tolerability profile and nearly all patients having disease control, the TiNivo study continues to underscore a compelling rationale for using a high-specificity VEGF inhibitor as the TKI of choice in immuno-oncology combinations," Doctor Bernard Escudier, MD, ex-Chairman of the Genitourinary Oncology Committee, Gustave Roussy, and lead investigator of the study. "The ability to give a VEGF inhibitor and immuno-oncology agent both at full dose and strength could serve to deliver both improved outcomes and an improved patient experience. I look forward to better understanding tivozanib’s potential in immunotherapy combinations through a larger randomized study, which is currently being planned."
"There are multiple cancers where IO-TKI combinations have demonstrated potential, and the favorable tolerability and efficacy outcomes seen in the TiNivo study make further exploration of these indications a priority for AVEO," said Michael Bailey, president and chief executive officer of AVEO. "We continue to build out a clinical strategy for studying such combinations, and look forward to outlining our plans following reporting of topline data from our Phase 3 TIVO-3 study, which is expected in the mid-fourth quarter."
"The data arising from combination studies with checkpoint inhibitors demonstrate the considerable potential for tivozanib in metastatic RCC," said Lee Morley, Chief Executive Officer of EUSA Pharma. "EUSA continues to launch tivozanib across the EU in line with its EMA approval as monotherapy in the first line setting where its efficacy and favorable tolerability profile continue to provide benefits to patients, and we are excited by the prospect of further development of tivozanib as part of a future IO-TKI treatment option."
About Tivozanib (FOTIVDA)
Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (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.1,2 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.3 As part of a North American registration plan, tivozanib is currently being studied in the Phase 3 TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory RCC. Tivozanib has been investigated in several tumors types, including renal cell, hepatocellular, colorectal and breast cancers.