ESMO 2026 | ctDNA analysis of KEYNOTE-412 in locally advanced head and neck cancer

So you know that the Keynote 412 trial compared chemoradiation plus placebo versus chemoradiation plus pembrolizumab for the treatment of locally advanced endemic cancer. And this trial did not meet its primary endpoint although with the long-term follow-up we are seeing a meaningful EFS benefit. But in this trial, we took plasma samples at baseline and during chemoradiation at week five, and we analyzed these plasma samples for ctDNA with a tumor-informed signature assay. So what we are showing, indeed, when you have high baseline ctDNA levels, it is prognostic in the HPV negative patient, but it was not prognostic in the HPV positive patient included in this trial. One of the reasons not being positive in HPV could be indeed that we included only T4 and N3 patients. And after we looked at the kinetics, so we looked at the patients that cleared ctDNA at week five during chemoradiation, and what we are seeing in HPV negative patients, we are seeing indeed that when you clear ctDNA, the prognosis is also clearly better with a five-year survival in the pembrolizumab arm of 72 percent, which is indeed very good. In HPV positive, with the clearance, the thing was less clear, less clear because we have fewer patients, but in the placebo arm of the trial also, it was linked with better EFS and OS.

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