Dr Choueiri on Trials in Progress in Advanced Renal Cell Carcinoma

Toni K. Choueiri, MD, director, Lank Center for Genitourinary Oncology, director, Kidney Cancer Center, senior physician, Dana-Farber Cancer Institute, Jerome and Nancy Kohlberg Chair and Professor of Medicine, Harvard Medical School, discusses ongoing trials in advanced renal cell carcinoma (RCC).

A phase 1/2 trial (NCT05119335) is evaluating NKT2152 in patients with advanced clear cell RCC. NKT2152 is a novel HIF2α inhibitor that demonstrated preclinical activity in xenograft models and cell lines. The phase 1 portion of the study has completed, and investigators are expecting to launch the dose-escalation portion soon. The primary end point of the study is to identify the maximum tolerated dose, and secondary end points include efficacy end points, such as response rate, and pharmacodynamic and pharmacokinetic analyses. The significance of the study is two-fold, according to Choueiri, who says that the trial has the potential to confirm the activity of NKT2152 in advanced clear cell RCC and set the stage for future combinational approaches. 

The phase 3 SAMETA trial (NCT05043090) is evaluating savolitinib in combination with durvalumab (Imfinzi) vs sunitinib (Sutent) and durvalumab monotherapy in patients with MET-driven, unresectable, locally advanced or metastatic papillary RCC. Previous research from the phase 2 CALYPSO trial (NCT02819596) demonstrated that the combination of savolitinib and durvalumab has activity in patients with MET-positive disease. MET-positive tumors represent between 30% and 40% of cases, representing an ideal target for therapy, Choueiri explains. Sunitinib was selected as the control arm because the study is expecting to accrue patients internationally, where cabozantinib (Cabometyx) either is not available or is not accepted as standard of care in this population, Choueiri says.

Previously, the phase 2 PAPMET trial (NCT02761057), which was conducted in patients with unselected papillary RCC, failed to show an overall survival benefit, despite showing improved progression-free survival and response rates with cabozantinib vs sunitinib, Choueiri says.