Broad utility of ultrasensitive analysis of ctDNA dynamics across solid tumors treated with immunotherapy

These data support the publication tentatively titled "Broad utility of ultrasensitive analysis of ctDNA dynamics across solid tumors treated with immunotherapy", and provided all necessary code and processed data to reproduce analysis and figures contained within the manusript.

Abstract

Immune checkpoint inhibitors (ICI) are widely prescribed to treat cancer, but the development of reliable biomarkers to predict ICI response across various cancer types remains challenging. To address this, we used ultrasensitive, patient-specific circulating tumor DNA (ctDNA) testing to study 202 patients (136 in the primary cohort, 66 in a validation cohort) with refractory metastatic pan-solid tumors (24 cancer types), receiving ICI, bispecific antibodies, or immune cell engagers in phase I trials. Ultrasensitive ctDNA analysis served as an early biomarker of improved clinical outcome as early as 21 days after treatment initiation (PreC2). Densely sampled longitudinal ctDNA (1455 plasma samples, averaging 7.2 per patient) showed that ctDNA clearance at any point correlated with radiological response and prolonged survival. Additionally, ctDNA trajectories distinguished true tumor progression from pseudoprogression and predicted outcome of immunotherapy treatment continued beyond progression. These findings, validated in the independent cohort, demonstrate the broad clinical utility of ultrasensitive ctDNA monitoring in immunotherapy-treated cancer patients.