Clinical Trials

Date: 2017-02-23

Type of information: DSMB assessment

phase: 3

Announcement: DSMB assessment

Company: Aveo Oncology (USA - MA)

Product: tivozanib (N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N´-(5-methyl-3-isoxazolyl) urea hydrochloride monohydrate)

Action mechanism: kinase inhibitor/tyrosine kinase inhibitor. Tivozanib is an oral, potent, selective inhibitor of vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) with a long half-life and activity against all three VEGF receptors.

Disease: renal cell carcinoma (RCC)

Therapeutic area: Cancer - Oncology

Country:

Trial details: The Phase 3 TIVO-3 trial is a pivotal, randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma. The trial is expected to enroll approximately 322 patients with recurrent RCC who have failed at least two prior regimens, including VEGFR-TKI therapy (other than sorafenib). Eligible patients may also have received checkpoint inhibitor therapy in earlier lines of treatment. Patients will be 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. The TIVO-3 trial, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support a first and third line indication for tivozanib in the U.S. Marketing authorization applications seeking approval of tivozanib as a treatment for first line renal cell cancer are currently pending in Europe and Russia based on applications submitted by Aveo’s partners EUSA Pharma and Pharmstandard in those respective territories.

Latest news:

•  • On February 23, 2017, Aveo Oncology announced that the Phase 3 TIVO-3 trial has successfully completed the first safety review by the study’s Safety Monitoring Committee (SMC). The SMC concluded that no safety concern was observed for tivozanib and recommended that the study replace the small number of patients who dropped out prior to starting treatment.
• The TIVO-3 trial is enrolling substantially ahead of schedule, and with the SMC recommendation to replace early dropouts the Company still expects to complete enrollment in June 2017, ahead of its prior guidance of August 2017. A pre-planned futility analysis of the trial is expected around midyear 2017, with topline data expected in the first quarter of 2018.
• • On February 9, 2017, Aveo Oncology announced clinical and regulatory updates for tivozanib. The pivotal, Phase 3 TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC), is enrolling substantially ahead of schedule.
• • On May 26, 2016, Aveo Oncology  announced that the first patient has been dosed in the Company’s pivotal TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC). The Phase 3 trial is expected to enroll approximately 322 patients with recurrent or metastatic RCC who have failed at least two prior regimens, including VEGFR-TKI therapy (other than sorafenib). Eligible patients may also have received checkpoint inhibitor therapy in earlier lines of treatment. Patients will be 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.
• • On May 20, 2015, Aveo Oncology announced  that it has received a written response from the FDA stating that a phase 3 study outlined by the Company, in patients with RCC who have failed at least two prior regimens, including VEGF therapy, “may support AVEO’s proposed indication for tivozanib in the 3rd line setting.” In response to whether the study, together with the TIVO-1 study, would be sufficient to support licensure of tivozanib as a treatment for advanced RCC, the FDA indicated: “whether the results from this [third line] study can support AVEO’s proposal for tivozanib in the first line setting is a review issue.” The study design shared with the FDA is a randomized, controlled, multi-center, open-label Phase 3 study of approximately 314 subjects randomized 1:1 to receive either tivozanib or sorafenib. Subjects enrolled in the study may include those who have received prior immunotherapy, including immune checkpoint (PD-1) inhibitors, reflecting a potentially evolving treatment landscape. The primary objective of the study would be PFS. Secondary objectives would include OS and objective response rate (ORR) as well as safety and pharmacokinetic endpoints.

Is general: Yes