Rationale for the Phase 3 COSMIC-313 Study in RCC

Toni Choueiri, MD, director Lank Center for Genitourinary Oncology, director, Kidney Cancer Center, and senior physician at Dana-Farber Cancer Institute as well as a Jerome and Nancy Kohlberg chair and professor of Medicine, Harvard Medical School, explains what led to the phase 3 COSMIC-313 clinical trial.

In COSMIC-313, the cabozantinib (Cabometyx; cabo) will be combined with the immunotherapy doublet nivolumab (Opdivo; nivo) and ipilimumab (Yervoy; ipi) to treat patients with previously untreated advanced or metastatic renal cell carcinoma.

The study is being conducted on 840 patients across 167 locations in North America, South America, Europe, Asia, and Oceania.

Transcription:

0:07| First, the rationale of combining these 3 drugs ipilimumab the anti-CTLA 4 [agent] nivolumab, the PD-1 inhibitor and cabozantinib, the TKI that targets essentially VEGF receptor, but also targets other kinases involved in resistance, all of these drugs have approval in renal cell carcinoma. Cabozantinib [is approved] as a single agent in refractory disease, nivolumab as a single-agent in refractory disease, and cabozantinib as a first-line treatment in intermediate and poor risk [disease]. And ipilimumab’s role in renal cell cancer is first-line in combination with nivolumab. So naturally, you want to combine them all and there is some safety data that came from Dr. Apollo from the National Cancer Institute that showed that 3 of them could be combinable with cabozantinib at 40 milligrams a day.

1:10 | So, the rationale was to you know, look at the modern control arm and that will be nivolumab ipilimumab and cabozantinib. So, it's a phase 3 trial randomized to nivo/ipi/cabo versus nivo/ipi placebo with 1 to 1 randomization. The primary endpoint is progression-free survival and the usual suspects as secondary end points are response rate, safety, quality-of-life, and others.