Evidence map›Paper›PMID 42149426›Full record

ArticleInvestigational new drugs2026

Preclinical and clinical evaluation of futibatinib in combination with binimetinib in patients with advanced cancer.

Jordi Rodon, Bert O'Neil, Christopher Lim, Natraj R Ammakkanavar, Carlos Torrado, Kazuaki Matsuoka, Hiroshi Hirai, Akihiro Miura, Bailey Anderson, Leah Jin and 4 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Investigational new drugs, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04965818 (A Phase 1b/2 Open-label, Nonrandomized Study of FGFR Inhibitor Futibatinib in Combination With MEK-inhibitor Binimetinib in Patients With Advanced KRAS Mutant Cancer), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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.

NCT04965818 phase1terminatednot on this map

A Phase 1b/2 Open-label, Nonrandomized Study of FGFR Inhibitor Futibatinib in Combination With MEK-inhibitor Binimetinib in Patients With Advanced KRAS Mutant Cancer

TypeinterventionalSponsorTaiho Oncology, Inc.Ran2021 to 2023Enrolled38ConditionsAdvanced or Metastatic Solid Tumors Irrespective of Gene Alterations, Non-Small Cell Lung Cancer, KRAS Gene MutationArmsFutibatinib and Binimetinib
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Jordi RodonMD Anderson Cancer Center, Houston, TX, USA. JRodon@mdanderson.org.
Bert O'NeilCommunity Health Network, Indianapolis, IN, USA.
Christopher LimDivision of Hematology-Oncology, UCLA, Los Angeles, CA, USA.
Natraj R AmmakkanavarCommunity Health Network, Indianapolis, IN, USA.
Carlos TorradoMD Anderson Cancer Center, Houston, TX, USA.
Kazuaki MatsuokaTaiho Pharmaceutical Co. Ltd, Chiyoda-Ku, Tokyo, Japan.
Hiroshi HiraiTaiho Pharmaceutical Co. Ltd, Chiyoda-Ku, Tokyo, Japan.
Akihiro MiuraTaiho Pharmaceutical Co. Ltd, Chiyoda-Ku, Tokyo, Japan.
Bailey AndersonTaiho Oncology, Inc., Princeton, NJ, USA.
Leah JinTaiho Oncology, Inc., Princeton, NJ, USA.
Nanae HangaiTaiho Oncology, Inc., Princeton, NJ, USA.
Amanda LongTaiho Oncology, Inc., Princeton, NJ, USA.
Volker WacheckTaiho Oncology, Inc., Princeton, NJ, USA.
Lee RosenDivision of Hematology-Oncology, UCLA, Los Angeles, CA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionKRAS-mutant NSCLC resistance to MEK inhibitors (MEKi) is related to compensatory upregulation of fibroblast growth factor receptor (FGFR) signaling. Futibatinib is a potent, covalent FGFR1-4 inhibitor approved for locally advanced/metastatic cholangiocarcinoma with FGFR2 fusions. We conducted a bench-to-bedside study evaluating futibatinib plus the MEKi binimetinib preclinically, followed by a Phase Ib trial of patients with advanced cancer.

methodsThe effect of futibatinib ± MEKi on cell signaling and proliferation of KRASmt NSCLC lines (A549, LU99) were assessed in vitro. In a Phase Ib study, patients with advanced cancer who had exhausted standard therapies received futibatinib QD plus binimetinib BID orally following a "3 + 3" dose-escalation design. Primary objective was to establish the recommended Phase 2 dose (RP2D) based on safety. Secondary endpoints included pharmacokinetics and anti-tumor activity.

resultsIn vitro, MEKi with futibatinib resulted in additive or synergistic anti-tumor activity in KRASmt NSCLC lines. Twenty-three patients received futibatinib with binimetinib at 4 dose levels. The most prevalent adverse events were reversible retinopathies in 20 patients, including 2 DLTs and limiting dose escalation beyond futibatinib 16 mg QD plus binimetinib 15 mg BID (MTD). There were no relevant drug-drug interactions between binimetinib and futibatinib. One patient harboring an FGFR2 fusion had a partial response. No RP2D could be defined as the MTD was below active dose levels of binimetinib.

conclusionDespite additive anti-tumor activity for FGFR and MEK inhibition in KRASmt NSCLC lines, the trial was stopped after dose escalation, as no RP2D was identified for futibatinib/binimetinib due to reversible retinopathies. Trial register number. NCT04965818. Trial registration date. 20-September-2021.

Indexed as

Antineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesCarcinoma, Non-Small-Cell LungLung NeoplasmsNaphthalenesProtein Kinase InhibitorsPyrimidinesAdultAgedCell Line, TumorCell ProliferationFemaleHumansMaleMiddle AgedAntineoplastic AgentsBenzimidazolesbinimetinibfutibatinibNaphthalenesProtein Kinase InhibitorsPyrazolesPyrimidinesPyrrolesBinimetinibFGFRFutibatinibMEKNon-small cell lung cancer

Identifiers

PMID42149426
PMCPMC13486011

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