Multinational phase 2 trial of first-line pembrolizumab for advanced renal cell carcinoma: final results from KEYNOTE-427

The multinational phase 2 KEYNOTE-427 trial showed antitumor activity with first-line pembrolizumab monotherapy in advanced clear cell renal cell carcinoma (ccRCC; cohort A) and non-clear cell renal cell carcinoma (nccRCC; cohort B). Final results from the trial have now been published. After a median follow-up of 61.1 months (range 54.7-65.5) in cohort A and 56.7 montyhs (47.9-64.0) in cohort B, the objective response rates (ORRs) by blinded independent central review were 36.4% and 26.7%, respectively. Continuous T-cell inflamed gene expression profile was positively associated with ORR in cohort A (p=0.0208) and cohort B (p=0.0021). Continuous PD-L1 combined positive score was positively associated with ORR (p=0.0195) and progression-free survival (PFS; p=0.0307) in cohort A and ORR (p<0.0001), PFS (p=0.0002) and overall survival (OS; p=0.0014) in cohort B. RCC driver gene mutation showed no consistent patterns with ORR in either cohort. In cohort A, participants with detectable ctDNA at baseline had shorter OS than participants with ctDNA-negative status: median 30.5 months (95% CI 18.1-56.4) versus 53.7 months (28.7-NR). The authors conclude that first-line pembrolizumab is active in ccRCC and nccRCC.