With the Phase 1 dose-escalating stage of the TiNivo trial (NCT03136627) completed, patients are being enrolled for the Phase 2 stage. It will evaluate the therapy’s effectiveness against advanced renal cell carcinoma and patients’ ability to tolerate it.
Tivozanib, formerly known as AV-951, inhibits the vascular endothelial growth factor receptor (VEGFR), which regulates blood vessel growth. Overproduction of the factor is a major driver of kidney cancer.
TiNivo hopes tivozanib can counter several kinds of solid tumors, including renal cell, colorectal, and breast cancers.
“VEGF-PD-1 combinations have yielded promising tumor response outcomes in renal cell cancer, yet the data presented to date point to challenging or prohibitive toxicity,” Michael Bailey, president and chief executive officer of AVEO, said in a press release. “We believe tivozanib offers a unique opportunity to potentially overcome this barrier.”
During the Phase 1 dose-escalating stage of the trial, six patients with kidney cancer were randomly assigned to receive one of two doses of tivozanib and a fixed dose of Opdivo every two weeks. The combination was well tolerated, with no tivozanib-related toxicities reported.
The Phase 1 results prompted researchers to select a dose of 1.5 mg of tivozanib a day for 21 days, followed by a seven-day rest period, as the regimen for the Phase 2 stage. The company expects to enroll about 20 participants in the Phase 2 component.
“Tivozanib has a uniquely favorable tolerability profile as demonstrated in past single agent and combination studies,” Dr. Bernard Escudier, chairman of the Genitourinary Oncology Committee at the Institut Gustave Roussy in Villejuif, France, said in a press release.
“These initial results are very promising in that we see both evidence of a uniquely tolerable combination as well as early and meaningful activity,” added Escudier, the lead researcher in the trial. “I look forward to enrolling the expansion [Phase 2] cohort and to establishing a broader understanding for the potential of this compelling combination.”
AVEO has asked the European Medicines Agency to approve tivonanib as a first-line treatment for advanced kidney cancer. The agency’s Committee for Medicinal Products for Human Use is reviewing the application. If it recommends approval, the request will go to the full agency and then the European Commission.
The drug is also being evaluated in the Phase 3 TIVO-3 clinical trial (NCT02627963). Positive results in that trial would help support an application for U.S. approval of tivonanib.
“As our registration strategy for single-agent tivozanib reaches key inflection points, with a European regulatory decision expected in the near term and readout of our U.S.-registration-directed TIVO-3 study expected in the first quarter of 2018, our attention is increasing on tivozanib immuno-oncology combinations that have the potential to deliver significantly improved outcomes and tolerability to patients,” said Michael Bailey, president and chief executive officer of AVEO. “The TiNivo trial is an important first step in this effort, and we share Dr. Escudier’s enthusiasm for the completion of this trial.”