ideasIdea
A short pre-surgery drug window as the default early test of new agents
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.
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.
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.
What would test it
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
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
3
Bottlenecks it attacks
- Trial design, endpoints and cost · A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.
- The valley of death between lab and product · Most academic discoveries die before anyone tests them in people because nobody funds the middle step.
- 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.