Research & Development
Aveo Oncology Touts Phase 3 TIVO-3 Trial of Tivozanib in Renal Cell Carcinoma Meets Primary Endpoint
8 November 2018 - - US-based Aveo Oncology (NASDAQ: AVEO) has received positive topline results from the primary analysis of the TIVO-3 trial, the company's Phase 3 randomised, controlled, multi-center, open-label study to compare tivozanib (FOTIVDA) to sorafenib in 351 subjects with highly refractory advanced or metastatic renal cell carcinoma, the company said.

The trial met its primary endpoint of demonstrating a statistically significant benefit in progression-free survival. Tivozanib demonstrated a 44% improvement in median PFS and 26% reduction in risk of progression or death (Hazard Ratio [HR]=0.74, p=0.02).

Median PFS was 5.6 months for tivozanib compared to 3.9 months for sorafenib. The TIVO-3 trial enrolled patients with RCC who have failed at least two prior regimens.

Among these, approximately 26% of patients received checkpoint inhibitor therapy in earlier lines of treatment.

Tivozanib PFS was longer than sorafenib both in patients who received prior checkpoint inhibitor therapy and those who did not.

The analysis of the secondary endpoint of overall survival was not mature at the time of the final PFS analysis, with only 46% of potential OS events having been reported.

At the time of the preliminary OS analysis, no statistically significant difference in OS was observed (HR=1.06, p=0.69). The final survival analysis per protocol is planned for August 2019, two years following the last patient enrolled.

Detailed results of the trial will also be submitted for presentation at an upcoming major medical meeting.

The secondary endpoint of overall response rate for patients receiving tivozanib was 18% compared to 8% for patients receiving sorafenib (p=0.02).

Tivozanib was generally well-tolerated, with grade 3 or higher adverse events consistent with those observed in previous tivozanib trials. Infrequent but severe adverse events reported in greater number in the tivozanib arm were thrombotic events similar to those observed in previous tivozanib studies.

The most common adverse event in patients receiving tivozanib was hypertension, an adverse event known to reflect effective VEGF pathway inhibition.

Based on results from the TIVO-3 trial, together with the previously completed Phase 3 TIVO-1 trial of tivozanib in the first line treatment of RCC, the company's goal is to submit a New Drug Application to the US Food and Drug Administration in approximately six months.

The TIVO-3 trial was designed to enroll patients with RCC who have failed at least two prior regimens, including VEGFR-TKI therapy.

Eligible patients may also have received checkpoint inhibitor therapy in earlier lines of treatment.

Patients are randomized 1: 1 to receive either tivozanib or sorafenib, with no crossover between arms.

The primary endpoint of the study is progression free survival. Secondary endpoints include overall survival, overall response rate, and safety and tolerability.

TIVO-3, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support a regulatory submission of tivozanib in the US as a treatment for RCC in multiple lines of therapy. TIVO-3 patients were exclusively enrolled in North America, Western Europe, and Central Europe.

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor tyrosine kinase inhibitor 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.

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.

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

Aveo Pharmaceuticals is a biopharmaceutical company dedicated to advancing a broad portfolio of targeted medicines for oncology and other areas of unmet medical need.

The company's strategy is to retain North American rights to its oncology portfolio while securing partners in development and commercialisation outside of North America. The company is seeking to develop and commercialize its lead candidate tivozanib in North America as a treatment for advanced or metastatic renal cell carcinoma.

The company has outlicensed tivozanib (FOTIVDA) for oncology in Europe and other territories outside of North America.

Tivozanib is approved in the European Union, as well as Norway and Iceland, for the first-line treatment of adult patients with RCC and for adult patients who are vascular endothelial growth factor receptor and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for RCC.

The company has entered into partnerships for the development and commercialization of AV-203 (CAN017) and ficlatuzumab, both clinical stage assets in oncology.

Aveo Oncology is currently seeking a partner to develop the AV-353 platform, a preclinical asset, worldwide for the potential treatment of pulmonary arterial hypertension.

The company has recently regained the rights to its AV-380 programme for the potential treatment of cachexia and is considering a variety of options to advance the program's development.


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