ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026
Investigating Early Kinetics in Plasma ctDNA and Peripheral T-cell Receptor Repertoire to Predict Treatment Outcomes to PD-1 Inhibitors in Head and Neck Squamous Cell Carcinoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04606940 (Study of Circulating Tumor DNA), which is not on this map. Not yet cited in PubMed.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Study of Circulating Tumor DNA (ctDNA) Kinetics in Immuno-oncology: Intense Dynamic Monitoring of ctDNA in Advanced/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Patients Treated With Immune Checkpoint Inhibitors.
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Authors and funding
20 authors.
Funding
Abstract
purposeImmune checkpoint blockade (ICB) therapies targeting the PD-1 axis have significantly improved survival in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Circulating tumor DNA (ctDNA) and peripheral T-cell receptor (TCR) repertoires are emerging as promising biomarkers for predicting ICB response. Early characterization of ctDNA and TCR dynamics may enable timely treatment adjustments before clinical or radiologic progression. EXPERIMENTAL
designThe IO-KIN study (NCT04606940) is a single-center, prospective trial involving 15 patients with R/M HNSCC treated with nivolumab or pembrolizumab. Blood samples (n = 104) were collected across seven time points from baseline to day 29. ctDNA was analyzed using a personalized assay (Signatera), and peripheral TCR repertoires were profiled using CapTCR-seq in eight patients.
resultsA decline in ctDNA after day 8 was associated with radiologic response, longer progression-free survival, and a trend toward improved overall survival. TCR repertoires transiently diversified between days 8 and 22, with longer diversification windows in patients showing sustained ctDNA decline. Using the GLIPHII algorithm, an Epstein-Barr virus-specific TCR signature was identified and persisted in patients with clinical benefit. Additional TCR signatures, potentially recognizing tumor-associated antigens, emerged as early as day 3 and were linked to positive outcomes.
conclusionsSimultaneous early monitoring of ctDNA and TCR dynamics reveals key determinants of ICB outcomes in R/M HNSCC. The transient nature of TCR diversification emphasizes the importance of precise sample timing to guide early therapeutic decisions and improve patient outcomes.
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