ArticleBritish journal of cancer2019
A phase Ib dose-finding, pharmacokinetic study of the focal adhesion kinase inhibitor GSK2256098 and trametinib in patients with advanced solid tumours.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01938443 (A Phase 1b, Multi-center, Open-label, Dose Escalation Study of GSK2256098), which is not on this map. Cited by 55 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.
A Phase 1b, Multi-center, Open-label, Dose Escalation Study of GSK2256098 (FAK Inhibitor) in Combination With Trametinib (MEK Inhibitor) in Subjects With Advanced Solid Tumors
Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Relevance of humanized three-dimensional tumor tissue models: a descriptive systematic literature review.Cellular and molecular life sciences : CMLS · 2020Pooled it
- Review
- Disarming cancer resistance: FAK as a therapeutic target.Trends in cancer · 2026Review
- Homoharringtonine exhibits senotherapeutic activity that mitigates diet- and age-associated obesity and insulin resistance and extends lifespan in mice.Nature communications · 2026Article
- Targeting Cytoskeleton and Cell Motility: Past and Novel Strategies for Cancer Therapy.Oncology research · 2026Review
- Targeting Tumor-Associated Macrophages to Reshape the Immuno-Mechanical Landscape: Molecular Mechanisms and Therapeutic Strategies.International journal of biological sciences · 2026Review
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- SOX10 Regulates Melanoma Metastasis Through the IRF1-ITGA3/EphA2-FAK Pathway.Cancer science · 2025Article
- Defactinib with avutometinib in patients with solid tumors: the phase 1 FRAME trial.Nature medicine · 2025Article
- Targeting Focal Adhesion Kinase in Lung Diseases: Current Progress and Future Directions.Biomolecules · 2025Review
- Drug Combinations Targeting FAK and MEK Overcomes Tumor Heterogeneity in Glioblastoma.Pharmaceutics · 2025Article
- Focal adhesion kinase (FAK): emerging target for drug-resistant malignant tumors.Molecular biology reports · 2025Review
- Evaluation of anti-liver cancer activity and anticancer mechanism of one novel small molecule compound (THY-10A62) targeting FAK pathway.Frontiers in oncology · 2025Article
- Article
- Mechanism and application of feedback loops formed by mechanotransduction and histone modifications.Genes & diseases · 2024Review
- FAK-LINC01089 negative regulatory loop controls chemoresistance and progression of small cell lung cancer.Oncogene · 2024Article
- Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin β1.Journal of translational medicine · 2024Article
- Roles and inhibitors of FAK in cancer: current advances and future directions.Frontiers in pharmacology · 2024Review
- Clinical Next Generation Sequencing Application in Mesothelioma: Finding a Golden Needle in the Haystack.Cancers · 2023Review
- Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells.Cell death & disease · 2023Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
backgroundCombined focal adhesion kinase (FAK) and MEK inhibition may provide greater anticancer effect than FAK monotherapy.
methodsThis dose-finding phase Ib study (adaptive 3 + 3 design) determined the maximum tolerated dose (MTD) of trametinib and the FAK inhibitor GSK2256098 in combination. Eligible patients had mesothelioma or other solid tumours with probable mitogen activated protein kinase pathway activation. Adverse events (AEs), dose-limiting toxicities, disease progression and pharmacokinetics/pharmacodynamics were analysed.
resultsThirty-four subjects were enrolled. The GSK2256098/trametinib MTDs were 500 mg twice daily (BID)/0.375 mg once daily (QD) (high/low) and 250 mg BID/0.5 mg QD (low/high). The most common AEs were nausea, diarrhoea, decreased appetite, pruritus, fatigue and rash; none were grade 4. Systemic exposure to trametinib increased when co-administered with GSK2256098, versus trametinib monotherapy; GSK2256098 pharmacokinetics were unaffected by concomitant trametinib. Median progression-free survival (PFS) was 11.8 weeks (95% CI: 6.1-24.1) in subjects with mesothelioma and was longer with Merlin-negative versus Merlin-positive tumours (15.0 vs 7.3 weeks).
conclusionsTrametinib exposure increased when co-administered with GSK2256098, but not vice versa. Mesothelioma patients with loss of Merlin had longer PFS than subjects with wild-type, although support for efficacy with this combination was limited. Safety profiles were acceptable up to the MTD.
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