Dr. Choueiri on the Rationale for the COSMIC-313 Trial in Advanced RCC

Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology, director of the Kidney Cancer Center, and senior physician at Dana-Farber Cancer Institute, as well as the Jerome and Nancy Kohlberg chair and professor of medicine at Harvard Medical School, discusses the rationale for the phase 3 COSMIC-313 trial (NCT03937219) in advanced renal cell carcinoma (RCC).

The ongoing COSMIC-313 study is randomizing patients with previously untreated advanced or metastatic RCC 1:1 to the combination of ipilimumab (Yervoy), nivolumab (Opdivo), and cabozantinib (Cabometyx) or ipilimumab, nivolumab, and a cabozantinib-matched placebo, says Choueiri. The primary end point of the study is progression-free survival, with overall survival, overall response rate, safety, and quality of life serving as secondary end points.

Cabozantinib, a VEGF receptor targeting agent that can also target MET and AXL, is currently approved as a single agent for the treatment of patients with previously untreated advanced RCC, as well as for patients with relapsed/refractory disease.

Nivolumab, a PD-1 inhibitor, is approved as a single agent for patients with advanced RCC, and in combination with ipilimumab for patients with intermediate- and poor-risk advanced RCC.

Early data have shown that the triplet regimen, with cabozantinib dosed at 40 mg daily, is tolerable among this patient population, Choueiri says.

Notably, the COSMIC-313 trial is the first trial in RCC to utilize a modern control arm rather than sunitinib (Sutent), concludes Choueiri.