OnCo
ideasIdea

ctDNA-guided switching among FGFR inhibitors

Track FGFR2 resistance mutations in blood and switch to the next-generation inhibitor that still covers them, before the scan shows progression.

Polyclonal FGFR2 kinase-domain mutations emerge on pemigatinib and futibatinib and are detectable in cfDNA weeks before radiographic progression; tinengotinib and lirafugratinib retain activity against several of them.

Hypothesis
Serial ctDNA monitoring with pre-emptive switching to a resistance-mutation-covering FGFR inhibitor extends time on FGFR-directed therapy compared with switching at radiographic progression.
Rationale
Resistance mutations are drug-specific and predictable; molecular progression precedes clinical progression.
What would test it
Randomised phase 2: ctDNA-triggered switch vs standard imaging-triggered switch; endpoint time to chemotherapy.
Maturity
early clinical

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cancers

1
Biliary tract cancer (cholangiocarcinoma)

technologies

2
Liquid biopsy (ctDNA)Small-molecule kinase inhibitors

targets

1
FGFR2

drugs

3
ApprovedSmall-molecule irreversible kinase inhibitor (FGFR1-4)
Futibatinib · Lytgobi
ApprovedSmall-molecule kinase inhibitor (FGFR1-3)
Pemigatinib · Pemazyre
Phase 3Small-molecule multi-kinase inhibitor (FGFR1-3, VEGFR, Aurora, JAK)
Tinengotinib

terms

2
Circulating tumour DNA (ctDNA)FGFR2 fusions and rearrangements