Evidence map›Paper›PMID 41850040›Full record

Trial reportESMO open2026

Phase III trial of infigratinib versus gemcitabine/cisplatin in adults with advanced cholangiocarcinoma with FGFR2 gene fusion or rearrangement: results and reflections on early termination of PROOF 301.

G K Abou-Alfa, I Borbath, S Roychowdhury, L Goyal, A Lamarca, T Macarulla, R T Shroff, D-Y Oh, C Tamaş, D M Savastano and 5 more

Abstract readClinical Trial, Phase IIIRandomized Controlled TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in ESMO open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

G K Abou-AlfaMemorial Sloan Kettering Cancer Center, New York, USA; Weill Medical College at Cornell University, New York, USA; Trinity College Dublin, Dublin, Ireland. Electronic address: abou-alg@mskcc.org.
I BorbathCliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium.
S RoychowdhuryOhio State Comprehensive Cancer Center/James Cancer Hospital, Columbus, USA.
L GoyalDepartment of Medicine, Stanford Cancer Center, Palo Alto, USA; Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA.
A LamarcaFundacion Jimenez Diaz University Hospital, Madrid, Spain.
T MacarullaGastrointestinal and Endocrine Tumor Unit Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
R T ShroffDivision of Hematology/Oncology, University of Arizona Cancer Center, Tucson, USA.
D-Y OhSeoul National University Hospital, Cancer Research Institute and National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea.
C TamaşHelsinn Healthcare SA, Lugano, Switzerland.
D M SavastanoHelsinn Therapeutics US Inc., Iselin, USA.
D F van VeenhuyzenQED Therapeutics, BridgeBio Inc., San Francisco, USA.
C XuQED Therapeutics, BridgeBio Inc., San Francisco, USA.
E FreasQED Therapeutics, BridgeBio Inc., San Francisco, USA.
J SolanasQED Therapeutics, BridgeBio Inc., San Francisco, USA.
M M JavleDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundInfigratinib, an oral fibroblast growth factor receptor (FGFR) 1-3 inhibitor, showed clinical activity and manageable adverse events in the P2 CBGJ398X2204 study and was conditionally approved for adults with previously treated, unresectable, or metastatic cholangiocarcinoma (CCA) with FGFR2 fusion or other rearrangement. PROOF 301, reported in this article, is the confirmatory phase III trial of infigratinib versus gemcitabine plus cisplatin as first-line treatment of FGFR2-rearranged CCA. PATIENTS AND

methodsEligible adult patients were randomly assigned in a 2 : 1 ratio to infigratinib 125 mg on days 1-21 of a 28-day treatment cycle versus gemcitabine (1000 mg/m

resultsOver 40 months, 1127 patients were pre-screened at 120 sites, and 48 patients were randomly allocated to the study in a 2 : 1 ratio (29 to infigratinib, 19 to chemotherapy). With a target accrual of ∼300 patients, this study was terminated early due to poor accrual. Median PFS (95% confidence interval) by blinded independent central review (BICR) was 7.4 and 8.0 months with infigratinib and chemotherapy, respectively. The ORRs by BICR were 37.9% with infigratinib and 15.8% with chemotherapy. Grade 3-4 adverse events occurred in 79.3% and 58.8% patients treated with infigratinib and chemotherapy, respectively.

conclusionEarly termination limited the ability to draw definitive conclusions on the efficacy of infigratinib as first-line treatment of FGFR2-rearranged CCA. This study illustrates the challenges of powering confirmatory studies in biomarker-selected subpopulations of rare tumors and highlights the need for regulatory collaboration to develop pragmatic frameworks for assessing novel therapies in ultra-rare malignancies.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBile Duct NeoplasmsCholangiocarcinomaCisplatinDeoxycytidinePhenylurea CompoundsReceptor, Fibroblast Growth Factor, Type 2AdultAgedFemaleGemcitabineGene RearrangementHumansMaleMiddle AgedPyrimidinesCisplatinDeoxycytidineFGFR2 protein, humanGemcitabineinfigratinibPhenylurea CompoundsPyrimidinesReceptor, Fibroblast Growth Factor, Type 2cholangiocarcinomafibroblast growth factor receptor inhibitorinfigratinibtargeted therapy

Identifiers

PMID41850040
PMCPMC13015651

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.