On November 6, 2017 AVEO Oncology (NASDAQ:AVEO) and EUSA Pharma reported the presentation of promising results from the ongoing Phase 1 portion of the TiNivo study, a Phase 1/2 multicenter trial of tivozanib (FOTIVDA) in combination with Bristol-Myers Squibb’s nivolumab (OPDIVO), an immune checkpoint, or PD-1, inhibitor, for the treatment of advanced renal cell carcinoma (RCC) (Press release, AVEO, NOV 6, 2017, View Source;p=RssLanding&cat=news&id=2314412 [SID1234521570]). The results were presented on Friday, November 3, at the 16th International Kidney Cancer Symposium in Miami, in an oral presentation titled "TiNivo: A Phase Ib Dose Escalation Trial of Tivozanib and Nivolumab in Renal Cell Carcinoma" by Laurence Albiges, M.D., Ph.D., Head, Genitourinary Unit, Institute Gustave Roussy, and a lead investigator of the study. A copy of the presentation is available at www.aveooncology.com or further information can be obtained via EUSA Pharma Medical Information.
The Phase 1 portion of the trial enrolled six patients, three with previously untreated metastatic RCC and three who had received first-line treatment. RCC tumor histology included five clear cell (one with sarcomatoid features) and one papillary. Tivozanib was administered to patients in two escalating dose cohorts (1.0 mg/QD and 1.5 mg/QD) in combination with nivolumab at a constant 240 mg every 2 weeks. The combination was well tolerated to the full dose and schedule of single agent tivozanib, with no dose limiting toxicities. The most common adverse events (any grade) were hypertension, asthenia and decreased appetite. No grade 4 adverse events were reported. Two grade 3 events were reported beyond cycle 1 (stomatitis and increased ALT), which did not lead to study discontinuation and were managed concurrently. Unconfirmed best response to date includes a 67% (4/6) partial response (PR) rate and a 100% disease control rate (PR + stable disease). Enrollment of approximately 20 patients in the Phase 2 portion of the trial is ongoing.
"Combining VEGF TKIs and PD-1s holds the potential for synergistic activity against renal cell carcinoma, yet most such combinations demonstrate a high rate of toxicity in the clinic," said Dr. Albiges. "Tivozanib has several distinguishing properties that may enhance its ability to combine with checkpoint inhibitors, including a highest in-class selectivity for the VEGF-Receptor (types 1, 2 and 3), and therefore fewer off-target effects, and the ability to significantly reduce regulatory T cells, thereby enhancing immune activity against the tumor. Tivozanib’s favorable tolerability profile has been demonstrated against sorafenib in the pivotal TIVO-1 study, and early results from the TiNivo study show a tolerable combination and evidence of promising activity."
"We are encouraged by the preliminary tolerability and activity results from the TiNivo study, as we believe they begin to underscore the unique potential of tivozanib-immunotherapy combinations," said Michael Needle, M.D., chief medical officer of AVEO. "With immunotherapy combinations continuing to demonstrate improved outcomes in patients with RCC, it will become increasingly important to leverage the best-in-class VEGF therapies and immunotherapies to optimize efficacy and tolerability in defined populations within this disease. We believe tivozanib is well-positioned within this evolving landscape, and we look forward to presenting the Phase 2 portion of TiNivo in the first half of next year. We also anticipate moving into additional combination studies in the coming quarters."
Lee Morley, EUSA Pharma’s Chief Executive Officer said, "Following the recent European approval of tivozanib (FOTIVDA) for the first-line treatment of patients with advanced RCC, emerging data from the TiNivo study indicates the potential for tivozanib in the setting of combination treatment with immunotherapies. The initial results of the TiNivo study are promising and, in partnership with AVEO, we look forward to developing new and innovative options based on the unique profile of tivozanib which will be important for the future management of patients."
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 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 investigated in several tumors types, including renal cell, colorectal and breast cancers.