Dr. Tykodi on the KEYNOTE-427 Trial With Pembrolizumab in RCC

Scott S. Tykodi, MD, PhD, a physician with the Seattle Cancer Care Alliance, an associate professor within the Division of Medical Oncology at the University of Washington, and an associate professor of the Clinical Research Division, Fred Hutchinson Cancer Research Center, provides background to the phase 2 KEYNOTE-427 trial with pembrolizumab (Keytruda) in renal cell carcinoma (RCC).

KEYNOTE-427 is a single-arm frontline study of pembrolizumab monotherapy for advanced RCC,says Tykodi. Cohort A included patients with a clear-cell histology only, while cohort B included patients with non–clear cell disease, says Tykodi. Cohort A enrolled a total of 110 patients. The clinical outcomes have been presented previously and showed an objective response rate of 36%, which included 3 complete responses and a median progression-free survival of 7.1 months.

These are interesting data because this was the first study looking at monotherapy with an anti–PD-1 agent in kidney cancer, notes Tykodi. These results indicate that pembrolizumab is a highly effective drug, but it’simportant to recognize that the current FDA-approved frontline regimens are all doublets, such as PD-1 plus CTLA-4 blockade or PD-1/PD-L1 with a VEGF TKI.

Now, investigators have taken the data set with well-established clinical end points, dug a bit deeper, and looked for biomarkers that might identify which patients are most likely to respond to treatment, explains Tykodi.This was a popular topic at the 2020 ASCO Virtual Scientific Program, and many similar attempts to look at the large clinical databases for biomarker discovery were made, notes Tykodi.

One of the techniques was taking the tumor tissue, conducting RNA sequencing, then clustering the gene expression into coherent pathways, and looking to see whether there is a signature of a biological pathway that is associated with the outcomes data, concludes Tykodi.