^
    1m
    Fusion transcriptome landscape in Glioblastoma (SNO 2024)
    Comprehensive molecular profiling reveals that approximately 10% of IDH WT GBMs carry oncogenic fusions that may be therapeutic targets. Broad spectrum of observed fusions underscores the need for novel clinical trial designs to allow efficient enrollment for prospective testing of potential targeted agents.
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CDK4 (Cyclin-dependent kinase 4) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • SEC61G (SEC61 Translocon Subunit Gamma) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
    |
    TP53 mutation • EGFR mutation • NTRK1 fusion • NTRK2 fusion • MET amplification • EGFR amplification • ALK fusion • ROS1 fusion • MET mutation • EGFRvIII mutation • FGFR3 fusion • IDH wild-type • EGFR fusion
    |
    MI Tumor Seek™
    8ms
    Bispecific T Cell Engager BRiTE for Patients With Grade IV Malignant Glioma (clinicaltrials.gov)
    P1, N=18, Not yet recruiting, Duke University | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026
    Trial completion date • Trial primary completion date • IO biomarker
    |
    EGFR mutation • EGFRvIII mutation
    9ms
    Plasma ctDNA liquid biopsy of IDH1, TERTp, and EGFRvIII mutations in glioma. (PubMed, Neurooncol Adv)
    Total cfDNA may also assist with prognostic information. Further studies are needed to validate these findings and the clinical role of ctDNA in glioma.
    Journal • Liquid biopsy • Circulating tumor DNA • Biopsy
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    EGFR mutation • IDH1 mutation • EGFRvIII mutation • TERT mutation
    1year
    Blockage of EGFR/AKT and mevalonate pathways synergize the antitumor effect of temozolomide by reprogramming energy metabolism in glioblastoma. (PubMed, Cancer Commun (Lond))
    Our findings not only uncovered the mechanism of metabolic reprogramming in EGFR-activated GBM but also provided a combinatorial therapeutic strategy for clinical GBM management.
    Journal
    |
    ACSL3 (Acyl-CoA Synthetase Long Chain Family Member 3)
    |
    EGFR mutation • EGFR amplification • EGFR overexpression • EGFRvIII mutation
    |
    Tagrisso (osimertinib) • temozolomide • MK-2206 • lovastatin
    1year
    Efficacy of WSD0922-Fu in osimertinib-resistant NSCLC with central nervous system (CNS) metastases – Updates from the dose escalation cohort of a first-in-human phase 1 clinical trial (MC1914) (SNO 2023)
    All patients with HGA received prior radiation and temozolomide. Furthermore, prolonged stable disease (9 cycles) was observed in a patient with EGFRvIII mutant GBM. Expansion cohorts are in progress to optimize WSD0922-Fu dose and schedule for future phase 2 development.
    Clinical • P1 data
    |
    EGFR mutation • EGFRvIII mutation
    |
    Tagrisso (osimertinib) • temozolomide • WSD0922
    1year
    Improved overall survival of recurrent glioblastoma (GBM) patients with EGFR amplification and EGFR vIII mutations treated with osimertinib: a retrospective review (SNO 2023)
    We conducted a retrospective review of rGBM patients with EGFR amplification and EGFRvIII mutations who received osimertinib in addition to other therapies such as bevacizumab, irinotecan, tumor-treating fields, and salvage radiation at recurrence. Despite the limitations of a retrospective study and small sample size, osimertinib is a promising targeted therapy for rGBM. Further research is warranted in a clinical trial to evaluate this treatment prospectively.
    Retrospective data • Review
    |
    EGFR (Epidermal growth factor receptor) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    EGFR mutation • EGFR amplification • EGFRvIII mutation • IDH wild-type
    |
    Avastin (bevacizumab) • Tagrisso (osimertinib) • irinotecan
    1year
    Targeting Cancer Stem Cells with a CDK2 Inhibitor in Glioblastoma (SNO 2023)
    Importantly, we found that the compound inhibited the self-renewal and growth of BTSCs in EGFRvIII subtype of BTSCs. This research has led to future investigation on in vivo assessment of this CDK2 inhibitor in combination with ionizing radiation and chemotherapy in preclinical models of GB.
    Cancer stem
    |
    OSMR (Oncostatin M Receptor)
    |
    EGFR mutation • EGFRvIII mutation
    1year
    Longitudinal analysis of serum-derived extracellular vesicle RNA to monitor dacomitinib treatment response in EGFR-amplified recurrent glioblastoma patients. (PubMed, Neurooncol Adv)
    Further analysis revealed genetic enrichment that enables stratification of responders from nonresponders prior to dacomitinib treatment as well as following administration. This study demonstrates that genetic composition analysis of serum EVs may aid in therapeutic stratification to identify patients with dacomitinib-responsive GBM.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR amplification • EGFRvIII mutation
    |
    Vizimpro (dacomitinib)
    over1year
    Evaluating Gene Fusions in Solid Tumors by Next- Generation Sequencing: A Tertiary Centre Experience (AMP Europe 2023)
    "Gene fusions represent crucial targets in the context of precision medicine. NGS testing for fusion detection not only allows analysis of multiple targets but also saves time and material. The identification of novel fusions in this study also highlights the potential for future therapeutic targets."
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • DCTN1 (Dynactin Subunit 1) • AGK (Acylglycerol Kinase) • SDC4 (Syndecan 4) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    EGFR mutation • NTRK1 fusion • MET exon 14 mutation • ROS1 positive • EGFRvIII mutation • FGFR1 fusion • FGFR3 fusion • LMNA-NTRK1 fusion • SDC4-ROS1 fusion • NTRK fusion
    |
    SOPHiA DDM™ Solid Tumor Plus Solution
    over1year
    WSD0922-FU for the Treatment of Glioblastoma, Anaplastic Astrocytoma, or Non-small Cell Lung Cancer With Central Nervous System Metastases (clinicaltrials.gov)
    P1, N=51, Recruiting, Mayo Clinic | N=77 --> 51
    Enrollment change
    |
    EGFR mutation • EGFR L858R • EGFR T790M • EGFR amplification • EGFR L861Q • EGFR C797S • EGFRvIII mutation • EGFR G719A • IDH wild-type
    |
    WSD0922
    over1year
    Intellance1: A Study of ABT-414 in Participants With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification (clinicaltrials.gov)
    P3, N=691, Completed, AbbVie | Phase classification: P2/3 --> P3
    Phase classification
    |
    EGFR (Epidermal growth factor receptor) • MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    EGFR mutation • EGFR amplification • EGFRvIII mutation
    |
    temozolomide • depatuxizumab mafodotin (ABT-414)
    over1year
    Driver mutations dictate the immunological landscape and response to checkpoint immunotherapy of glioblastoma. (PubMed, Cancer Immunol Res)
    Pharmacologic targeting of this axis induced a systemic decrease in the numbers of PMN-MDSC, facilitated responses to PD-1 and CTLA4 combination checkpoint blocking immunotherapy, and prolonged survival in mice bearing EGFRvIII-driven GBM. Our results uncover a relationship between cancer driver mutations, TIME composition and sensitivity to checkpoint blockade in GBM and support the stratification of patients with GBM for checkpoint blockade therapy based on integrated genotypic and immunological profiles.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • CXCR2 (Chemokine (C-X-C motif) receptor 2) • CXCL1 (Chemokine (C-X-C motif) ligand 1)
    |
    EGFR mutation • EGFR expression • EGFR wild-type • EGFRvIII mutation
    over1year
    CARv3-TEAM-E T Cells in Glioblastoma (clinicaltrials.gov)
    P1, N=21, Recruiting, Marcela V. Maus, M.D.,Ph.D. | Not yet recruiting --> Recruiting | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jan 2024 --> Jun 2025
    Enrollment open • Trial completion date • Trial primary completion date
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    EGFR amplification • EGFRvIII mutation
    |
    CARv3-TEAM-E T cells
    over1year
    Structure-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation of EGFR for the Clinical Treatment of Glioblastoma. (PubMed, Appl Biochem Biotechnol)
    The pre-existing pharmaceutical lapatinib (PubChem ID: 208,908) with a higher affinity score is used for virtual screening...Both compounds are equivalent, according to the ADMET study. This report implies that the virtual screened chemical could be a promising Glioblastoma therapy.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFRvIII mutation
    |
    lapatinib
    almost2years
    In vivo efficacy and metabolism of a new synthetized dual EGFR-DNA targeting combi-molecule in a human stem cells-derived model of glioblastoma implanted intracranially in mice (AACR 2023)
    The existing treatment (chemotherapy with temozolomide (TMZ)+radiotherapy) increases the median survival by 2-3 months...Conclusion. The results in toto suggest that the intact structure of AF143 is stable to metabolism, can cross the blood brain barrier and induce antitumour activity in a EGFRvIII expressing glioblastoma stem cell model.
    Preclinical
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR expression • EGFRvIII mutation • EGFRvIII expression
    |
    temozolomide
    almost2years
    G2 checkpoint targeting via Wee1 inhibition radiosensitizes EGFRvIII-positive glioblastoma cells. (PubMed, Radiat Oncol)
    We conclude that the inhibition of Wee1 is an effective targeting approach for the radiosensitization of both EGFRvIII- and EGFRvIII+ GBM cells and may therefore represent a promising new therapeutic option to increase response to radiotherapy.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • WEE1 (WEE1 G2 Checkpoint Kinase)
    |
    EGFR mutation • EGFRvIII mutation • EGFR negative • TP53 expression • EGFRvIII expression
    |
    adavosertib (AZD1775)
    almost2years
    Immunotherapy as a New Therapeutic Approach for Brain and Spinal Cord Tumors. (PubMed, Adv Exp Med Biol)
    With respect to cancer vaccines, rindopepimut has been well-studied in glioblastoma (GBM) patients with the EGFRvIII mutation, with early results from phase II trials showing possible efficacy in carefully selected GBM patients...However, it is important to keep in mind that the field is still in its infancy and many clinical trials are still early-phase. Several, clinical trials are currently underway to further explore the role of immunotherapy for CNS malignancies.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • IL2 (Interleukin 2)
    |
    EGFR mutation • HER-2 mutation • EGFRvIII mutation
    |
    Rintega (rindopepimut)
    almost2years
    CARv3-TEAM-E T Cells in Glioblastoma (clinicaltrials.gov)
    P1, N=21, Not yet recruiting, Marcela V. Maus, M.D.,Ph.D.
    New P1 trial
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    EGFR amplification • EGFRvIII mutation
    |
    CARv3-TEAM-E T cells
    2years
    Identification of a novel peptide ligand for the cancer-specific receptor mutation EGFRvIII using high-throughput sequencing of phage-selected peptides. (PubMed, Sci Rep)
    Additionally, computational docking analysis suggested that the identified peptide binds selectively to EGFRvIII. The novel VLGREEWSTSYW peptide is thus a promising EGFRvIII-targeting agent for future applications in cancer diagnosis and therapy.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR expression • EGFR wild-type • EGFRvIII mutation • EGFRvIII expression
    2years
    Targeted profiling of human extrachromosomal DNA by CRISPR-CATCH. (PubMed, Nat Genet)
    CRISPR-CATCH followed by nanopore sequencing enabled single-molecule ecDNA methylation profiling and revealed hypomethylation of the EGFR promoter on ecDNAs. We distinguished heterogeneous ecDNA species within the same sample by size and sequence with base-pair resolution and discovered functionally specialized ecDNAs that amplify select enhancers or oncogene-coding sequences.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR2 (Fibroblast growth factor receptor 2)
    |
    EGFR mutation • EGFRvIII mutation
    2years
    TAS2940, a Novel Brain-Penetrable Pan-ERBB Inhibitor, for Tumors with HER2 and EGFR Aberrations. (PubMed, Cancer Sci)
    TAS2940 has promising therapeutic effects in preclinical study against cancers harboring HER2/EGFR mutations, especially metastatic and primary brain tumors. Our results highlight potential novel strategies against lung cancers with brain metastases harboring HER2/EGFR ex20 insertions and glioblastomas with EGFR aberrations.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • HER-2 amplification • HER-2 expression • EGFR exon 20 insertion • EGFR expression • HER-2 exon 20 insertion • EGFR exon 20 mutation • EGFRvIII mutation
    |
    TAS2940
    2years
    A novel EGFRvIII-T cell bispecific antibody for the treatment of glioblastoma. (PubMed, Mol Cancer Ther)
    EGFRvIII-TCB induced tumor regression in GBM animal models, including humanized orthotopic GBM patient-derived xenograft (PDX) models. Our results warrant the clinical testing of EGFRvIII-TCB for the treatment of EGFRvIII-expressing GBMs.
    Journal • IO biomarker
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFRvIII mutation • EGFRvIII expression
    2years
    Highly sensitive EGFRvIII detection in circulating extracellular vesicle RNA of glioma patients. (PubMed, Clin Cancer Res)
    This study demonstrates the feasibility of detecting EGFRvIII mutation in plasma using a highly sensitive and specific ddPCR assay. We also show a higher than previously reported EGFRvIII prevalence in glioma tumor tissue. Several features of the assay are favorable for clinical implementation for detection and monitoring of EGFRvIII positive tumors.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR amplification • EGFRvIII mutation
    over2years
    Convection enhanced delivery of EGFR targeting antibody-drug conjugates Serclutamab talirine and Depatux-M in glioblastoma patient-derived xenografts. (PubMed, Neurooncol Adv)
    CED of Depatux-M is well tolerated and results in extended survival in orthotopic GBM PDXs. In contrast, CED of Ser-T was associated with a much narrower therapeutic window.
    Journal
    |
    GFAP (Glial Fibrillary Acidic Protein)
    |
    EGFR mutation • EGFR amplification • EGFRvIII mutation
    |
    serclutamab talirine (ABBV-321) • depatuxizumab mafodotin (ABT-414)
    over2years
    Epidermal Growth Factor Receptor Variant III Mutation, an Emerging Molecular Marker in Glioblastoma Multiforme Patients: A Single Institution Study on the Indian Population. (PubMed, Cureus)
    Temozolomide, an oral alkylating agent, is currently the most commonly used chemotherapy...Conclusions Thus, the identification of this mutation would segregate patients who may benefit from newer therapeutic approaches. In the future, personalized treatment may be advised for GBM patients depending on the presence of the EGFRvIII mutation.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR positive • EGFRvIII mutation
    |
    temozolomide
    over2years
    Novel Cyclic Peptides for Targeting EGFR and EGRvIII Mutation for Drug Delivery. (PubMed, Pharmaceutics)
    The conjugates were more cytotoxic to EGFR+ve cells than free CPT. Our results describe a novel cyclic peptide, which can be used for targeted drug delivery to cells overexpressing the EGFR and EGFRvIII mutation.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR overexpression • EGFR positive • EGFRvIII mutation • EGFRvIII expression
    over2years
    Depatuxizumab-mafodotin in EGFR-amplified newly diagnosed glioblastoma: a phase III randomized clinical trial. (PubMed, Neuro Oncol)
    Interim analysis demonstrated no OS benefit for depatux-m in treating EGFR-amp newly diagnosed GBM. No new important safety risks were identified.
    Clinical • P3 data • Journal
    |
    EGFR (Epidermal growth factor receptor) • MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    EGFR mutation • EGFR amplification • EGFR overexpression • EGFRvIII mutation
    |
    temozolomide • depatuxizumab mafodotin (ABT-414)
    over2years
    Distribution and favorable prognostic implication of genomic EGFR alterations in IDH-wildtype glioblastoma. (PubMed, Cancer Med)
    We found that the EGFR gene profiles of GBM differ among cohorts and that EGFR alterations are good prognostic markers of overall survival in patients with IDH-wildtype GBM. Additionally, we identified rare EGFR variants with longitudinal and temporal transformations of EGFRvIII.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR amplification • EGFRvIII mutation • IDH wild-type
    |
    OncoPanel™ Assay
    over2years
    Intellance1: A Study of ABT-414 in Participants With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification (clinicaltrials.gov)
    P2/3, N=655, Completed, AbbVie | Active, not recruiting --> Completed
    Trial completion
    |
    EGFR (Epidermal growth factor receptor) • MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    EGFR mutation • EGFR amplification • EGFRvIII mutation
    |
    temozolomide • depatuxizumab mafodotin (ABT-414)
    almost3years
    Intellance1: A Study of ABT-414 in Participants With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification (clinicaltrials.gov)
    P2/3, N=655, Active, not recruiting, AbbVie | Trial completion date: Dec 2021 --> Jun 2022 | Trial primary completion date: Dec 2021 --> Jun 2022
    Clinical • Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    EGFR mutation • EGFR amplification • EGFRvIII mutation
    |
    temozolomide • depatuxizumab mafodotin (ABT-414)
    3years
    Preliminary results of the neratinib arm in the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): a phase II platform trial using Bayesian adaptive randomization (SNO 2021)
    METHODS Patients with newly diagnosed MGMT-unmethylated glioblastoma were randomized to receive either radiotherapy with concomitant and adjuvant temozolomide or standard radiochemotherapy followed by adjuvant neratinib (240 mg daily). However, there was no significant improvement in OS in EGFR amplified/mutated patients (HR 1.05; p-value 0.87) between neratinib (median 14.2) compared to the control arm (median 14.6). CONCLUSION Neratinib prolonged PFS in the EGFR positive subpopulation but there was no overall PFS benefit, or any OS improvement.
    Clinical • P2 data
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    EGFR mutation • EGFR amplification • EGFRvIII mutation
    |
    temozolomide • Nerlynx (neratinib)
    3years
    Development of 5-ALA based liquid biopsy for the non-invasive diagnosis of glioblastoma (SNO 2021)
    We identified several mRNAs including Gli3, STAG2, ELF3, PHLPP1 which play an important role in cancer. CONCLUSION The ability to sort and characterize tumor specific PpIX EVs following 5-ALA administration opens new avenues for liquid biopsy-based glioma diagnosis.
    Liquid biopsy
    |
    EGFR (Epidermal growth factor receptor) • STAG2 (Stromal Antigen 2) • PHLPP1 (PH Domain And Leucine Rich Repeat Protein Phosphatase 1) • ELF3 (E74 Like ETS Transcription Factor 3) • GLI3 (GLI Family Zinc Finger 3)
    |
    EGFR mutation • EGFRvIII mutation
    3years
    The EGFRvIII transcriptome in glioblastoma, a meta-omics analysis. (PubMed, Neuro Oncol)
    These data provide deeper insights into the complex EGFRvIII biology and provide new insights for targeting EGFRvIII mutated tumours.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
    |
    EGFR mutation • EGFR amplification • EGFR expression • MDM2 amplification • CDK4 amplification • EGFRvIII mutation • EGFRvIII expression
    3years
    Autophagy inhibition by TSSC4 (tumor suppressing subtransferable candidate 4) contributes to sustainable cancer cell growth. (PubMed, Autophagy)
    Finally, TSSC4 suppresses tumorsphere formation and tumor growth by inhibiting autophagy and maintaining cell survival in tumorspheres. Taken together, sustainable cancer cell growth can be achieved by autophagy inhibition via TSSC4 expression.ABBREVIATIONS: 3-MA: 3-methyladenine; ACTB: actin beta; CQ: chloroquine; EGFRvIII: epidermal growth factor receptor variant III; ERBB2: erb-b2 receptor tyrosine kinase 2; GBM: glioblastoma multiforme; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule Associated protein 1 light chain 3; TSSC4: tumor suppressing subtransferable candidate 4.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TYK2 (Tyrosine Kinase 2)
    |
    EGFR mutation • EGFRvIII mutation • EGFRvIII expression
    |
    chloroquine phosphate
    over3years
    Efficacy of osimertinib plus bevacizumab in glioblastoma patients with simultaneous EGFR amplification and EGFRvIII mutation. (PubMed, J Neurooncol)
    While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.
    Clinical • Journal
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    EGFR mutation • MET amplification • EGFR amplification • EGFRvIII mutation
    |
    Avastin (bevacizumab) • Tagrisso (osimertinib) • temozolomide
    over3years
    Intellance1: A Study of ABT-414 in Participants With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification (clinicaltrials.gov)
    P2/3, N=640, Active, not recruiting, AbbVie | Trial primary completion date: Jun 2021 --> Dec 2021
    Clinical • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    EGFR mutation • EGFR amplification • EGFRvIII mutation
    |
    temozolomide • depatuxizumab mafodotin (ABT-414)