{"entity":{"id":"idea-tr2-pdl1-digital-calibration","kind":"idea","name":"One digital PD-L1 scale that maps across all the competing assays","aka":[],"tldr":"There are several different PD-L1 tests, each tied to a different drug, and they disagree. A single digitally calibrated scale would let any lab's result be translated into any drug's cut-off.","summary":"22C3, SP263, 28-8 and SP142 assays, with tumour proportion score, combined positive score and immune-cell scoring, produce different positivity for the same tumour. The Blueprint project showed partial concordance. A quantitative digital pathology reference (stain intensity and cell counts calibrated on shared reference materials) could express each assay on a common scale, so a lab running one assay could report validated equivalents for the cut-offs used in each drug label.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["paige","pathai"],"cancers":[],"sections":[],"technologies":["digital-pathology-ai","histopathology-ihc","checkpoint-inhibitor"],"targets":["pdl1"],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-immunotherapy-response"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A calibrated digital PD-L1 score will predict benefit from PD-1 blockade at least as well as each label-specified assay in retrospective analyses of trial samples, allowing a single test to serve multiple drugs.","rationale":"Digital quantification removes reader variability, and reference materials remove staining variability, the two dominant sources of disagreement.","test":"Stain trial samples from two registrational immunotherapy trials with all four assays plus the digital scale; compare predictive performance against outcomes.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},"route":"/ideas/idea-tr2-pdl1-digital-calibration/","neighbours":{"company":[{"id":"paige","kind":"company","name":"Paige AI","route":"/companies/paige/"},{"id":"pathai","kind":"company","name":"PathAI","route":"/companies/pathai/"}],"technology":[{"id":"digital-pathology-ai","kind":"technology","name":"Digital pathology & AI","route":"/technologies/digital-pathology-ai/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"paper":[{"id":"paper-fernandez-jama-oncol","kind":"paper","name":"Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue","route":"/key-papers/paper-fernandez-jama-oncol/"}],"idea":[{"id":"idea-tr2-label-assay-concordance","kind":"idea","name":"Drug labels must state which biomarker assays were validated and how they compare","route":"/ideas/idea-tr2-label-assay-concordance/"},{"id":"idea-tr2-open-cdx-validation-sets","kind":"idea","name":"Public gold-standard datasets for validating every cancer biomarker test","route":"/ideas/idea-tr2-open-cdx-validation-sets/"}]}}