ArticleThe oncologist2019
A Phase I Study of Binimetinib (MEK162) Combined with Pexidartinib (PLX3397) in Patients with Advanced Gastrointestinal Stromal Tumor.
Article in The oncologist, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Pexidartinib, a Novel Small Molecule CSF-1R Inhibitor in Use for Tenosynovial Giant Cell Tumor: A Systematic Review of Pre-Clinical and Clinical Development.Drug design, development and therapy · 2020Pooled it
- Precision therapeutic strategies for advanced gastrointestinal stromal tumors.Cancer metastasis reviews · 2026Review
- Why precision oncology works: lessons from gastrointestinal stromal tumours.Exploration of targeted anti-tumor therapy · 2026Review
- Targeting tumor-associated macrophages to overcome immune checkpoint inhibitor resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Review
- Design and Synthesis of Pyridine-Based Pyrrolo[2,3-Pharmaceuticals (Basel, Switzerland) · 2025Article
- Genetic predisposition in sarcomas: clinical implications and management.EClinicalMedicine · 2025Review
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Insights into CSF-1/CSF-1R signaling: the role of macrophage in radiotherapy.Frontiers in immunology · 2025Review
- How to Use Macrophages Against Cancer.Cells · 2024Review
- Macrophages as Potential Therapeutic Targets in Acute Myeloid Leukemia.Biomedicines · 2024Review
- KIT ATP-Binding Pocket/Activation Loop Mutations in GI Stromal Tumor: Emerging Mechanisms of Kinase Inhibitor Escape.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Article
- Mechanistic studies of tumor-associated macrophage immunotherapy.Frontiers in immunology · 2024Review
- Drugs in the GIST Field (Therapeutic Targets and Clinical Trial Staging).Current drug delivery · 2024Article
- Molecular Advances in the Treatment of Advanced Gastrointestinal Stromal Tumor.The oncologist · 2023Review
- Identification of shared characteristics in tumor-infiltrating T cells across 15 cancers.Molecular therapy. Nucleic acids · 2023Article
- Tumor microenvironment signaling and therapeutics in cancer progression.Cancer communications (London, England) · 2023Review
- Article
- In Vivo Evaluation of Fibroblast Growth Factor Receptor Inhibition in Mouse Xenograft Models of Gastrointestinal Stromal Tumor.Biomedicines · 2022Article
- An overview of agents and treatments for PDGFRA-mutated gastrointestinal stromal tumors.Frontiers in oncology · 2022Review
- Gastrointestinal Stromal Tumors (GISTs): Novel Therapeutic Strategies with Immunotherapy and Small Molecules.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
lessons learnedThe combination of pexidartinib and binimetinib was safe and tolerable and demonstrated encouraging signs of efficacy in two patients with advanced gastrointestinal stromal tumor (GIST) refractory to tyrosine kinase inhibitors (TKIs).Molecular profiling of GISTs at diagnosis and upon progression may provide insight into the mechanisms of response or resistance to targeted therapies.Additional trials are needed to further explore combined KIT and MEK inhibition in treatment-naïve and TKI-refractory patients with advanced GIST.
backgroundNearly all patients with advanced gastrointestinal stromal tumor (GIST) develop resistance to imatinib, and subsequent treatments have limited efficacy. Dual inhibition of KIT and MAPK pathways has synergistic antitumor activity in preclinical GIST models.
methodsThis was an investigator-initiated, phase I, dose escalation study of the MEK inhibitor binimetinib combined with pexidartinib, a potent inhibitor of CSF1R, KIT, and FLT3, in patients with advanced or metastatic GIST who progressed on imatinib. The primary endpoint was phase II dose determination; secondary endpoints included safety, tolerability, and efficacy. An expansion cohort to further evaluate safety and efficacy was planned.
resultsTwo patients were treated at dose level one (binimetinib 30 mg b.i.d. and pexidartinib 400 mg every morning and 200 mg every evening), after which the study was terminated by the manufacturer. No dose-limiting toxicities (DLTs) were reported, and treatment was well tolerated. The only grade ≥3 treatment-emergent adverse event (TEAE) was asymptomatic elevated creatine phosphokinase (CPK). Both patients had a best response of stable disease (SD) by RECIST. Progression-free survival (PFS) and overall survival (OS) were 6.1 and 14.6 months, respectively, in one patient with five prior lines of therapy. The second patient with
conclusionPexidartinib combined with binimetinib was tolerable, and meaningful clinical activity was observed in two imatinib-refractory patients.
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Registered trials
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.