{"entity":{"id":"idea-tr2-window-of-opportunity-triplets","kind":"idea","name":"Two-week pre-operative windows to compare combination biology head to head","aka":[],"tldr":"Give patients a short course of one of several drug pairs in the gap before surgery and compare what happened inside the tumours. It is the fastest human test of whether a combination does anything.","summary":"Window-of-opportunity studies give a drug for 1 to 4 weeks between diagnosis and surgery and compare pre- and post-treatment tissue. Multi-arm windows randomising to several combinations with pharmacodynamic endpoints (proliferation, immune infiltration, target pathway suppression) can rank combinations by biological effect in under a year, before any efficacy trial.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["idea-tr2-neoadjuvant-combo-platform"],"cancers":["colorectal","head-and-neck"],"sections":[],"technologies":["single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-preclinical-models"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combinations ranked highest by pharmacodynamic effect in a multi-arm window study will have higher pathological response rates when taken forward into neoadjuvant trials than lower-ranked ones.","rationale":"Window studies with Ki67 changed endocrine therapy development in breast cancer (POETIC). Multi-arm windows with modern spatial and single-cell readouts can compare combinations mechanistically.","test":"A four-arm window study in resectable colorectal or head and neck cancer with paired biopsies, spatial transcriptomics and a pre-specified pharmacodynamic ranking; follow the top arm into a neoadjuvant trial.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},"route":"/ideas/idea-tr2-window-of-opportunity-triplets/","neighbours":{"idea":[{"id":"idea-tr2-neoadjuvant-combo-platform","kind":"idea","name":"Pre-surgery platform trials that test combinations on pathological response in months","route":"/ideas/idea-tr2-neoadjuvant-combo-platform/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"}],"technology":[{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"}],"bottleneck":[{"id":"b-preclinical-models","kind":"bottleneck","name":"Lab models that fail to predict what happens in patients","route":"/bottlenecks/b-preclinical-models/"},{"id":"b-combination-space","kind":"bottleneck","name":"Too many combinations to test","route":"/bottlenecks/b-combination-space/"}],"paper":[{"id":"paper-palmer-cell","kind":"paper","name":"Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy","route":"/key-papers/paper-palmer-cell/"}]}}