Scott Tykodi, MD, PhD, on Takeaways from KEYNOTE-427 in Renal Cell Carcinoma

Pembrolizumab (Keytruda) monotherapy appeared to be tolerable with promising antitumor activity in patients with clear cell renal cell carcinoma, according to an updated follow-up of cohort A in the KEYNOTE-427 trial presented at the 2020 ASCO Virtual Scientific Program.

Scott Tykodi, MD, PhD, a physician with the Seattle Cancer Care Alliance, and associate professor in the Division of Medical Oncology at University of Washington Medicine, and an associate professor in the Clinical Research Division at the Fred Hutchinson Cancer Research Center, spoke with CancerNetwork about the key takeaways from his presentation.

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One of the interesting observations in our data sets, and it's consistent across the other data sets, is the lack of an association of tumor mutational burden and neoantigen load in renal cell carcinoma with outcomes with the checkpoint blocking drugs. That association was made in lung cancer and melanoma a couple years ago, but we're really excited that people had a handle on what might be happening in those tumors: that it was tumor, immune recognition of neoantigens as perhaps being more robust higher ability T-cell interactions, that were really the driving force about why these drugs worked in those diseases.

And so that was the essential immune recognition and it's fed forward to vaccine programs that are geared towards augmenting neoantigen recognition and even engineered T-cell therapy compounds. There's a platform for harvesting TCRs from TIL that are thought to be neoantigen engaging and expand those therapeutically. Renal cell carcinoma doesn't seem to play by the same rules. The mutation density is less than for melanoma and for lung cancer, that are diseases that are chronically exposed to environmental carcinogen. So it doesn't mean that there can't be new antigen recognition, but it may not be a key driver. And we have to think more broadly about the repertoire of what T cells are actually encountering and recognizing. And so perhaps being a little bit circumspect about jumping into those sorts of therapy, platforms with renal cell carcinoma as perhaps not being the ideal tumor type, to look at those sorts of modalities.