# ctDNA-guided switching among FGFR inhibitors

Source: https://onco.cc/ideas/idea-btc-ctdna-fgfr-resistance/  
OnCo record `idea-btc-ctdna-fgfr-resistance` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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

## Summary

In biliary tract cancer driven by FGFR2 fusions, resistance to pemigatinib and futibatinib arises through polyclonal FGFR2 kinase-domain mutations that appear in cell-free DNA weeks before scans show progression. The idea is to monitor plasma ctDNA serially and switch pre-emptively to a next-generation inhibitor such as tinengotinib or lirafugratinib that still covers the emerging mutation. The rationale is that these resistance mutations are drug-specific and predictable, and molecular progression precedes clinical progression. The proposed test is a randomised phase 2 of ctDNA-triggered versus imaging-triggered switching with time to chemotherapy as the endpoint, at an early clinical stage, bearing on the liquid biopsy and kinase inhibitor technologies and the FGFR2 target.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- 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.
- Proposed test: Randomised phase 2: ctDNA-triggered switch vs standard imaging-triggered switch; endpoint time to chemotherapy.
- Maturity: early-clinical

## Sources

- ClinicalTrials.gov NCT02924376: FIGHT-202: https://clinicaltrials.gov/study/NCT02924376
- ClinicalTrials.gov NCT02052778: FOENIX-CCA2: https://clinicaltrials.gov/study/NCT02052778

## Connected records

- cancers: [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Intrahepatic cholangiocarcinoma](https://onco.cc/cancers/intrahepatic-cholangiocarcinoma/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [FGFR2](https://onco.cc/targets/fgfr2/)
- drugs: [Futibatinib](https://onco.cc/drugs/futibatinib/), [Pemigatinib](https://onco.cc/drugs/pemigatinib/), [Tinengotinib](https://onco.cc/drugs/tinengotinib/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [FGFR2 fusions and rearrangements](https://onco.cc/terms/fgfr2-fusion/)
- trials: [FIGHT-202](https://onco.cc/trials/fight-202/), [FIGHT-302](https://onco.cc/trials/fight-302/), [FIRST-308](https://onco.cc/trials/first-308/), [Futibatinib (TAS-120) in Patients With Advanced Biliary Tract Cancer](https://onco.cc/trials/nct07710885/), [Study of Tinengotinib VS. Physician's Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma](https://onco.cc/trials/nct05948475/)
- key papers: [Expanding Horizons in Cholangiocarcinoma: Emerging Targets Beyond FGFR2 and IDH1](https://onco.cc/key-papers/paper-fgfr2-cholangiocarcinoma-int-j-mol-sci-2025/), [FGFR2 Inhibition in Cholangiocarcinoma](https://onco.cc/key-papers/paper-fgfr2-cholangiocarcinoma-annu-rev-med-2023/), [FGFR2-Rearranged Biliary Tract Cancer: Biology, Resistance Mechanisms, and Emerging Therapeutic Strategies](https://onco.cc/key-papers/paper-fgfr2-cholangiocarcinoma-cancers-basel-2026/)
- ideas: [A ctDNA residual disease-guided adjuvant trial after gallbladder cancer resection](https://onco.cc/ideas/idea-gbc-ctdna-residual-disease-guided-adjuvant-trial/)

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