ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Phase I Study of the Novel Enhancer of Zeste Homolog 2 (EZH2) Inhibitor GSK2816126 in Patients with Advanced Hematologic and Solid Tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02082977 (A Phase I Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2816126 in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma, Transformed Follicular Lymphoma, Other Non-Hodgkin's Lymphomas, Solid Tumors and Multiple Myeloma), which is not on this map. Cited by 102 papers, 2 of them syntheses 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 I Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2816126 in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma, Transformed Follicular Lymphoma, Other Non-Hodgkin's Lymphomas, Solid Tumors and Multiple Myeloma
Who cites it
102 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pooled it
- Advances and Perspectives in the Treatment of T-PLL.Current hematologic malignancy reports · 2020Pooled it
- Structural characteristics and SARs of EZH2 inhibitors.Molecular diversity · 2026Review
- The Crosstalk Between Metabolic Reprogramming and Histone Methylation in Tumor Immunity and Immunotherapy.Cells · 2026Review
- Novel therapeutic targets at the crossroad between epigenetics and signal transduction pathways in B-cell lymphomas.Clinical and experimental medicine · 2026Review
- The Role of EZH2 ın Malıgnant Pleural Mesothelıoma and Beyond: Current Practıce and Future Perspectıves.Current oncology reports · 2026Review
- Chemical Epigenetics: Small Molecules Targeting Chromatin Modifiers in Disease Modulation.Cell biochemistry and biophysics · 2026Review
- Deciphering epigenetic crosstalk in multiple myeloma pathogenesis and treatment.Clinical epigenetics · 2026Review
- Therapeutic targeting of chromatin alterations in leukemia and solid tumors.International journal of cancer · 2026Review
- Molecular reprogramming in cutaneous melanoma: the central role of G9a and EZH2 methyltransferase inhibitors in tumor plasticity, immune evasion, and therapeutic resistance.Frontiers in pharmacology · 2026Review
- Prevention of cancer initiation by augmenting MHC-I antigen presentation via EZH2 inhibition.Oncogene · 2025Article
- Article
- Histone modifications in cervical cancer: Epigenetic mechanisms, functions and clinical implications (Review).Oncology reports · 2025Review
- Depleting the Action of EZH2 through PI3K-mTOR Inhibition to Overcome Metastasis and Immunotherapy Resistance in Triple-Negative Breast Cancer.Molecular cancer therapeutics · 2025Article
- Precision epigenetic therapies in oncology.Cancer metastasis reviews · 2025Review
- New frontiers in prostate cancer treatment from systemic therapy to targeted therapy.EMBO molecular medicine · 2025Review
- Multi-omics based and AI-driven drug repositioning for epigenetic therapy in female malignancies.Journal of translational medicine · 2025Review
- GSK343, an inhibitor of EZH2, prevents acquired cisplatin resistance in bladder cancer.Molecular genetics and genomics : MGG · 2025Article
- Immune Checkpoint Inhibitor Therapy for Prostate Cancer: Present and Future Prospectives.Biomolecules · 2025Review
- A targetable antioxidant defense mechanism to EZH2 inhibitors enhances tumor cell vulnerability to ferroptosis.Cell death & disease · 2025Article
42 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
20 authors.
Funding
Abstract
purposeEnhancer of zeste homolog 2 (EZH2) activity is dysregulated in many cancers. PATIENTS AND
methodsThis phase I study determined the safety, maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of the intravenously administered, highly selective EZH2 inhibitor, GSK2816126, (NCT02082977). Doses of GSK2816126 ranged from 50 to 3,000 mg twice weekly, and GSK2816126 was given 3-weeks-on/1-week-off in 28-day cycles. Eligible patients had solid tumors or B-cell lymphomas with no available standard treatment regimen.
resultsForty-one patients (21 solid tumors, 20 lymphoma) received treatment. All patients experienced ≥1 adverse event (AE). Fatigue [22 of 41 (53.7%)] and nausea [20 of 41 (48.8%)] were the most common toxicity. Twelve (32%) patients experienced a serious AE. Dose-limiting elevated liver transaminases occurred in 2 of 7 patients receiving 3,000 mg of GSK2816126; 2,400 mg was therefore established as the MTD. Following intravenous administration of 50 to 3,000 mg twice weekly, plasma GSK2816126 levels decreased biexponentially, with a mean terminal elimination half-life of approximately 27 hours. GSK2816126 exposure (maximum observed plasma concentration and area under the plasma-time curve) increased in a dose-proportional manner. No change from baseline in H3K27me3 was seen in peripheral blood mononuclear cells. Fourteen of 41 (34%) patients had radiological best response of stable disease, 1 patient with lymphoma achieved a partial response, 21 of 41 (51%) patients had progressive disease, and 5 patients were unevaluable for antitumor response.
conclusionsThe MTD of GSK2816126 was established at 2,400 mg, but the dosing method and relatively short half-life limited effective exposure, and modest anticancer activity was observed at tolerable doses.
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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.