{"entity":{"id":"idea-btc-ctdna-fgfr-resistance","kind":"idea","name":"ctDNA-guided switching among FGFR inhibitors","aka":[],"tldr":"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.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02924376: FIGHT-202","url":"https://clinicaltrials.gov/study/NCT02924376"},{"label":"ClinicalTrials.gov NCT02052778: FOENIX-CCA2","url":"https://clinicaltrials.gov/study/NCT02052778"}],"tags":[],"related":[],"cancers":["cholangiocarcinoma"],"sections":[],"technologies":["liquid-biopsy","kinase-inhibitors"],"targets":["fgfr2"],"drugs":["pemigatinib","futibatinib","tinengotinib"],"companies":[],"institutions":[],"pathways":[],"terms":["fgfr2-fusion","ctdna"],"trials":["fight-202","fight-302","first-308","nct05948475","nct07710885"],"people":[],"bottlenecks":[],"keyPapers":["paper-fgfr2-cholangiocarcinoma-annu-rev-med-2023","paper-fgfr2-cholangiocarcinoma-cancers-basel-2026","paper-fgfr2-cholangiocarcinoma-int-j-mol-sci-2025"],"journals":[],"dependsOn":[],"notes":[],"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.","test":"Randomised phase 2: ctDNA-triggered switch vs standard imaging-triggered switch; endpoint time to chemotherapy.","maturity":"early-clinical"},"route":"/ideas/idea-btc-ctdna-fgfr-resistance/","neighbours":{"cancer":[{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"intrahepatic-cholangiocarcinoma","kind":"cancer","name":"Intrahepatic cholangiocarcinoma","route":"/cancers/intrahepatic-cholangiocarcinoma/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"fgfr2","kind":"target","name":"FGFR2","route":"/targets/fgfr2/"}],"drug":[{"id":"futibatinib","kind":"drug","name":"Futibatinib","route":"/drugs/futibatinib/"},{"id":"pemigatinib","kind":"drug","name":"Pemigatinib","route":"/drugs/pemigatinib/"},{"id":"tinengotinib","kind":"drug","name":"Tinengotinib","route":"/drugs/tinengotinib/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"fgfr2-fusion","kind":"term","name":"FGFR2 fusions and rearrangements","route":"/terms/fgfr2-fusion/"}],"trial":[{"id":"fight-202","kind":"trial","name":"FIGHT-202","route":"/trials/fight-202/"},{"id":"fight-302","kind":"trial","name":"FIGHT-302","route":"/trials/fight-302/"},{"id":"first-308","kind":"trial","name":"FIRST-308","route":"/trials/first-308/"},{"id":"nct07710885","kind":"trial","name":"Futibatinib (TAS-120) in Patients With Advanced Biliary Tract Cancer","route":"/trials/nct07710885/"},{"id":"nct05948475","kind":"trial","name":"Study of Tinengotinib VS. Physician's Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma","route":"/trials/nct05948475/"}],"paper":[{"id":"paper-fgfr2-cholangiocarcinoma-int-j-mol-sci-2025","kind":"paper","name":"Expanding Horizons in Cholangiocarcinoma: Emerging Targets Beyond FGFR2 and IDH1","route":"/key-papers/paper-fgfr2-cholangiocarcinoma-int-j-mol-sci-2025/"},{"id":"paper-fgfr2-cholangiocarcinoma-annu-rev-med-2023","kind":"paper","name":"FGFR2 Inhibition in Cholangiocarcinoma","route":"/key-papers/paper-fgfr2-cholangiocarcinoma-annu-rev-med-2023/"},{"id":"paper-fgfr2-cholangiocarcinoma-cancers-basel-2026","kind":"paper","name":"FGFR2-Rearranged Biliary Tract Cancer: Biology, Resistance Mechanisms, and Emerging Therapeutic Strategies","route":"/key-papers/paper-fgfr2-cholangiocarcinoma-cancers-basel-2026/"}],"idea":[{"id":"idea-gbc-ctdna-residual-disease-guided-adjuvant-trial","kind":"idea","name":"A ctDNA residual disease-guided adjuvant trial after gallbladder cancer resection","route":"/ideas/idea-gbc-ctdna-residual-disease-guided-adjuvant-trial/"}]}}