# Two-week pre-operative windows to compare combination biology head to head

Source: https://onco.cc/ideas/idea-tr2-window-of-opportunity-triplets/  
OnCo record `idea-tr2-window-of-opportunity-triplets` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- 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): https://doi.org/10.1016/j.cell.2017.11.009

## Connected records

- ideas: [Pre-surgery platform trials that test combinations on pathological response in months](https://onco.cc/ideas/idea-tr2-neoadjuvant-combo-platform/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/)
- technologies: [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/)
- bottlenecks: [Lab models that fail to predict what happens in patients](https://onco.cc/bottlenecks/b-preclinical-models/), [Too many combinations to test](https://onco.cc/bottlenecks/b-combination-space/)
- key papers: [Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy](https://onco.cc/key-papers/paper-palmer-cell/)

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