Trial reportNeuro-oncology2016
Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study.
Open access · bronzeAbstract readClinical Trial, Phase IIMulticenter Study
In one paragraph
Trial report in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 396 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
396citing papers in PubMed, 4 pooled it
14.9field-weighted citation impact, top 1% of its field
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.
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
396 citing papers in PubMed, 4 syntheses or guidelines pooled it, 568 citations in OpenAlex.
- A systematic review of immunotherapy in high-grade glioma: learning from the past to shape future perspectives.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Pooled it
- Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements.International journal of molecular sciences · 2023Pooled it
- Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of targeted therapies and immunotherapies in the management of progressive glioblastoma.Journal of neuro-oncology · 2022Pooled it
- Cutting edges and therapeutic opportunities on tumor-associated macrophages in lung cancer.Frontiers in immunology · 2022Pooled it
- Article
- Glioma-induced DNMT3A reduction in microglia promotes an anti-tumoral phenotype.Cell death and differentiation · 2026Article
- Convection-enhanced delivery of dexamethasone in glioma models suppresses myeloid inflammation while avoiding systemic toxicities.The Journal of clinical investigation · 2026Article
- Microenvironment-derived acetylated amino acids promote glioblastoma treatment resistance.Research square · 2026Article
- Next-generation therapeutics for glioblastoma: Challenges and future directions.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Review
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- The intersection of chemokine signaling with the hallmarks of cancer in glioblastoma.Journal of neuro-oncology · 2026Review
- Immunotherapy for Glioma: A compartmental framework for resistance and rational combination design.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- The Invasive Margin of Glioblastoma as a Molecular Ecosystem: Spatial Heterogeneity, Tumor-Host Interactions, and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Macrophage Plasticity in Cancer Therapy: Function, Timing, and Tradeoffs.International journal of molecular sciences · 2026Review
- Lighting up Macrophage Reprogramming Assists Immunosuppressive Niche Modulation in Primary Tumors and Tumor-Draining Lymph Nodes of Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- NF1 Leucine Rich Domain-Derived Extracellular Vesicles Remodel the Glioblastoma Immune Microenvironment via an ADAM17-Associated Inflammatory Program.Journal of extracellular vesicles · 2026Article
- Overcoming resistance in glioblastoma immunotherapy: lessons from the past and opportunities for the future.Molecular biology reports · 2026Review
- Review
336 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 10 institutions in 1 country.
Nicholas ButowskiUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Howard ColmanUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
John F De GrootUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Antonio M OmuroUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Lakshmi NayakUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Patrick Y WenUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Timothy F CloughesyUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Adhirai MarimuthuUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Sam HaidarUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Arie PerryUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Jason HuseUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Joanna PhillipsUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Brian L WestUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Keith B NolopUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Henry H HsuUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Keith L LigonUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Annette M MolinaroUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
Michael PradosUniversity of California at San Francisco, San Francisco, California (N.B., A.P., J.P., A.M.M, M.P.); Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (H.C.); The University of Texas MD Anderson Cancer Center, Houston, Texas (J.F.D.G.); Department of Neurology, Memorial Sloan Kettering Cancer Hospital, New York, New York (A.M.O.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (L.N., P.Y.W., S.H., K.L.L.); UCLA Medical Center, Los Angeles, California (T.F.C.); Plexxikon Inc., Berkeley, California (A.M., B.L.W., K.B.N., H.H.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Pathology, Memorial Sloan Kettering Cancer Hospital, New York, New York (J.H.).
The University of Texas MD Anderson Cancer Center · USHuntsman Cancer Institute · USPlexxikon (United States)UCLA Medical Center · USBrigham and Women's Hospital · USCenter for Neuro-Oncology · USDana-Farber Brigham Cancer Center · USMemorial Sloan Kettering Cancer Center · USUniversity of California, San Francisco · USUniversity of Utah · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MTumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MTissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Susan M Chang · 2002 to 2026
$57.4MHeparan sulfate proteoglycans as critical regulators of brain cancer malignancyR01NS081117 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PHILLIPS, JOANNA · 2012 to 2016
$1.7MNCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA097257NINDS NIH HHS R01 NS081117
Abstract
backgroundThe colony stimulating factor 1 receptor (CSF1R) ligands, CSF1 and interleukin-34, and the KIT ligand, stem cell factor, are expressed in glioblastoma (GB). Microglia, macrophages, blood vessels, and tumor cells also express CSF1R, and depletion of the microglia reduces tumor burden and invasive capacity. PLX3397 is an oral, small molecule that selectively inhibits CSF1R and KIT, penetrates the blood-brain barrier in model systems, and represents a novel approach for clinical development.
methodsWe conducted a phase II study in patients with recurrent GB. The primary endpoint was 6-month progression-free survival (PFS6). Secondary endpoints included overall survival response rate, safety, and plasma/tumor tissue pharmacokinetics. Exploratory endpoints included pharmacodynamic measures of drug effect in blood and tumor tissue.
resultsA total of 37 patients were enrolled, with 13 treated prior to a planned surgical resection (Cohort 1) and 24 treated without surgery (Cohort 2). PLX3397 was given at an oral dose of 1000 mg daily and was well tolerated. The primary efficacy endpoint of PFS6 was only 8.6%, with no objective responses. Pharmacokinetic endpoints revealed a median maximal concentration (Cmax) of 8090 ng/mL, with a time to attain Cmax of 2 hour in plasma. Tumor tissue obtained after 7 days of drug exposure revealed a median drug level of 5500 ng/g. Pharmacodynamic changes included an increase in colony stimulating factor 1 and reduced CD14(dim)/CD16+ monocytes in plasma compared with pretreatment baseline values.
conclusionPLX3397 was well tolerated and readily crossed the blood-tumor barrier but showed no efficacy. Additional studies are ongoing, testing combination strategies and potential biomarkers to identify patients with greater likelihood of response.
Indexed as
Administration, OralAminopyridinesBiomarkers, TumorBlood-Brain BarrierBrain NeoplasmsCohort StudiesFemaleFollow-Up StudiesGlioblastomaHumansImmunoenzyme TechniquesMaleMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPrognosisAminopyridinesBiomarkers, TumorpexidartinibPyrrolesReceptors, Granulocyte-Macrophage Colony-Stimulating FactorCSF1RglioblastomagliomamicrogliaPLX3397
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