AVEO Oncology has announced that its phase 1/2 AVEO-sponsored TiNivo trial evaluating tivozanib in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, Opdivo (nivolumab), in subjects with advanced renal cell carcinoma (RCC) has progressed to the Phase 2 portion of the trial.

Advancement of the study into the phase 2 expansion follows the successful completion of the Phase 1 dose escalation portion of the trial, where tivozanib was administered in two escalating dose cohorts in combination with nivolumab at a constant 240 mg every 2 weeks (n=6). The combination was well tolerated to the full dose and schedule of single agent tivozanib, with no dose limiting toxicities. The full dose tivozanib regimen of 1.5 mg daily for 21 days, followed by a 7 day rest period, is the recommended Phase 2 dose (RP2D) for the expansion portion of the trial, which is expected to enroll up to an additional 20 subjects. The TiNivo study is being led by the Institut Gustave Roussy in Paris under the direction of Bernard Escudier, MD, Chairman of the Genitourinary Oncology Committee. phase 1 results from the ongoing study will be submitted for presentation at an upcoming scientific meeting.

“The promise of delivering synergistic activity by combining VEGF TKIs and PD-1s in renal cell carcinoma hinges on the tolerability of the combination,” said Dr. Escudier. “Tivozanib has a uniquely favorable tolerability profile as demonstrated in past single agent and combination studies. These initial results are very promising in that we see both evidence of a uniquely tolerable combination as well as early and meaningful activity. I look forward to enrolling the expansion cohort and to establishing a broader understanding for the potential of this compelling combination.”

“Together with the longest progression free survival from a Phase 3 first line RCC study, tivozanib’s tolerability is distinct from other VEGF TKIs, which we believe better position it for use in combination with immunotherapy and other agents,” said Michael Bailey, president and chief executive officer of AVEO. “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 US 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. The TiNivo trial is an important first step in this effort, and we share Dr. Escudier’s enthusiasm for the completion of this trial.”