OnCo
ideasIdea

Add a drug when the blood test turns, without stopping the one that works

When a resistance mutation first appears in the blood, the current drug is often still controlling most of the tumour. Adding a second drug rather than swapping may keep both under control.

Most ctDNA-guided strategies switch therapy at molecular progression. Because the resistant clone is usually a minority at that point, switching abandons control of the sensitive majority. An additive strategy keeps the backbone and adds a mechanism-matched agent when a specific resistance alteration crosses a threshold in plasma, with the aim of suppressing both populations.

Hypothesis
Mechanism-matched addition at molecular progression yields longer time to radiographic progression than either continuing alone or switching, in patients with a single dominant emergent mechanism.
Rationale
Combination at the point of minimal resistant burden is when the added agent has the best chance of eradicating the emergent clone, and the backbone still suppresses the dominant population.
What would test it
Three-arm randomised phase 2 at molecular progression on osimertinib with detectable MET amplification: continue, switch, or add a MET inhibitor; primary endpoint time to radiographic progression.
Maturity
speculative
Who has to act
clinic
Cost to try
Medium ($1M to $50M)
Years to first evidence
5
Bottlenecks it attacks

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