ideasIdea
One digital PD-L1 scale that maps across all the competing assays
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.
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.
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.
What would test it
Stain trial samples from two registrational immunotherapy trials with all four assays plus the digital scale; compare predictive performance against outcomes.
Maturity
early clinical
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
3
Bottlenecks it attacks
- Biomarkers are not validated or standardised · Tests that decide who gets a drug are often not validated prospectively and are measured differently in every lab.
- No one can predict who responds to immunotherapy · Checkpoint drugs cure some patients and do nothing for most. We still cannot tell the two apart before treating.