{"entity":{"id":"idea-tr1-window-of-opportunity-default","kind":"idea","name":"A short pre-surgery drug window as the default early test of new agents","aka":[],"tldr":"Between diagnosis and surgery there are usually a few weeks. Giving a new drug in that window and comparing the tumour before and after surgery shows whether it hits its target in real people, quickly and cheaply.","summary":"Window-of-opportunity trials give a short course of an investigational agent between diagnostic biopsy and definitive surgery, with paired tissue for pharmacodynamic, proliferation (Ki-67) and immune readouts, and ctDNA dynamics. The proposal is to make a window study a standard early step for agents with a tissue biomarker, with cancer centres maintaining a standing window-trial pathway (consent, scheduling, sample handling) that any agent can slot into.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":["breast-hr-positive","prostate","head-and-neck"],"sections":[],"technologies":["single-cell-spatial","histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","ctdna"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-translational-valley","b-biomarker-validation"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Agents showing target modulation in a window study will succeed in later phases at a higher rate than agents without such evidence, and window studies will kill inactive agents earlier and cheaper.","rationale":"Pre-surgical endocrine and CDK4/6 window studies predicted later trial outcomes through Ki-67 change; the design gives human pharmacodynamic proof-of-mechanism with 20-40 patients.","test":"Fund a standing window-trial pathway at five centres and track the correlation between window-study pharmacodynamic outcomes and subsequent phase 2 success for the agents tested.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},"route":"/ideas/idea-tr1-window-of-opportunity-default/","neighbours":{"cancer":[{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-translational-valley","kind":"bottleneck","name":"The valley of death between lab and product","route":"/bottlenecks/b-translational-valley/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"paper":[{"id":"paper-davis-bmj","kind":"paper","name":"Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13","route":"/key-papers/paper-davis-bmj/"}],"roadmap":[{"id":"surgery-roadmap","kind":"roadmap","name":"Surgery roadmap: radical operations → less surgery → no surgery when a drug has done the work","route":"/roadmaps/surgery-roadmap/"},{"id":"trial-modernisation-roadmap","kind":"roadmap","name":"Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on","route":"/roadmaps/trial-modernisation-roadmap/"}]}}