On September 23, 2019 AVEO Oncology (NASDAQ: AVEO) and EUSA Pharma reported the upcoming presentation of final results from the Phase 2 portion of the TiNivo study, a Phase 1b/2 multicenter trial of oral (PO) tivozanib (FOTIVDA), AVEO’s once-daily, potent and selective vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI), 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 (RCC) (Press release, AVEO, SEP 23, 2019, View Source [SID1234539713]). The results will be presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Annual Congress, in a poster presentation titled "TiNivo: Tivozanib combined with nivolumab results in prolonged progression free survival in patients with metastatic renal cell carcinoma (mRCC). Final Results." (Presentation 947P).
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The Phase 1b/2 study 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 and showed additive or synergistic activity for objective response rate and progression free survival (PFS) in both treatment naïve and previously treated patients with mRCC. Overall median PFS for the 25 patients treated at the study’s full dose and schedule was 18.9 months (95% CI: 16.4; NR). Median PFS for previously untreated patients (n=12) was 18.5 months, while median PFS for previously treated patients (n=13) has not yet been reached as of the August 27, 2019 data cutoff date. An objective response rate was observed in 56% of patients (complete responses + partial responses), including one treatment naïve patient (1/12) achieving a complete response, and disease control (complete response + partial response + stable disease) was observed in 96% of patients. The most common treatment-related Grade 3/4 adverse event was hypertension.
An abstract of these data is currently available via the ESMO (Free ESMO Whitepaper) 2019 Annual Congress website. A copy of the poster will be available following the presentation at www.aveooncology.com, or further information can be obtained via EUSA Pharma Medical Information.
"Tivozanib has shown a favorable adverse event profile, thanks to its unique selectivity, that we believe has the potential to make it the ideal candidate for combination with an immunotherapy, like nivolumab, in metastatic RCC," said Doctor Bernard Escudier, MD, ex-Chairman of the Genitourinary Oncology Committee, Gustave Roussy, and lead investigator of the study. "With considerable follow up now complete in the TiNivo study, the long median PFS suggests a favorable durability of response, particularly in the second line. I look forward to seeing this potential explored in a larger outcome study in the near future."
"We are pleased with the level of antitumor activity we are seeing with this combination both in treatment naive and previously treated patients," said Michael Bailey, president and chief executive officer of AVEO. "We believe these data highlight the potentially unique benefits of a tivozanib-immunotherapy combination in a refractory patient population, a setting in which conclusive immunotherapy-TKI combination studies have yet to be conducted. We look forward to working with our partners at EUSA to determine potential next steps for the tivozanib-immunotherapy combination."
"The data arising from combination studies with checkpoint inhibitors demonstrates the considerable potential for tivozanib in metastatic RCC," said Lee Morley, chief executive officer of EUSA Pharma. "EUSA continue to seek reimbursement and 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 continues to provide benefits to patients, and are excited by the prospect of further development of tivozanib as part of a future IO-TKI treatment option."
Presentation Details
Title: TiNivo: Tivozanib combined with nivolumab results in prolonged progression free survival in patients with metastatic renal cell carcinoma (mRCC). Final Results.
Presenter: Philippe Barthelemy, Medical Oncology Department, Hôpitaux Universitaires de Strasbourg, Strasbourg, FR
Presentation Number: 947P
Date and Time: September 30, 2019, 12:20 p.m. CEST
Location: Poster Area (Hall 4)
About Tivozanib
Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway, New Zealand 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 models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC4. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers.