Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2020
Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 50 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 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB054329 in Subjects With Advanced Malignancies
A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic Review of Epigenetic Therapies for Treatment of IDH-mutant Glioma.World neurosurgery · 2022Pooled it
- Prostate cancer epigenetics - from pathophysiology to clinical application.Nature reviews. Urology · 2025Review
- Targeting lysine acetylation readers and writers.Nature reviews. Drug discovery · 2025Review
- Recent Advancement in Drug Targeting Therapies in the Treatment of Pancreatic Cancer.Current pharmaceutical design · 2025Review
- BET inhibition revealed varying MYC dependency mechanisms independent of gene alterations in aggressive B-cell lymphomas.Clinical epigenetics · 2024Article
- Investigational drugs in early phase trials for myelofibrosis.Expert opinion on investigational drugs · 2024Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Bromodomain proteins as potential therapeutic targets for B-cell non-Hodgkin lymphoma.Cell & bioscience · 2024Review
- BRD4: an effective target for organ fibrosis.Biomarker research · 2024Review
- Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).Oncology reports · 2024Article
- Peptide Inhibitor Targeting the Extraterminal Domain in BRD4 Potently Suppresses Breast Cancer BothJournal of medicinal chemistry · 2024Article
- Review
- Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies.Journal of experimental & clinical cancer research : CR · 2024Review
- Super-enhancers and the super-enhancer reader BRD4: tumorigenic factors and therapeutic targets.Cell death discovery · 2023Review
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- The synergy of the XPO1 inhibitors combined with the BET inhibitor INCB057643 in high-grade B-cell lymphoma via downregulation of MYC expression.Scientific reports · 2023Article
- Metabolic Reprogramming by Ribitol Expands the Therapeutic Window of BETi JQ1 against Breast Cancer.Cancers · 2023Article
- Bromo- and Extra-Terminal Domain Inhibitors Induce Mitochondrial Stress in Pancreatic Ductal Adenocarcinoma.Molecular cancer therapeutics · 2023Article
- Targeting bromodomain-containing proteins: research advances of drug discovery.Molecular biomedicine · 2023Review
- BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas.Nature communications · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors.
Funding
Abstract
purposeBromodomain and extraterminal (BET) proteins are key epigenetic transcriptional regulators, inhibition of which may suppress oncogene expression. We report results from 2 independent first-in-human phase 1/2 dose-escalation and expansion, safety and tolerability studies of BET inhibitors INCB054329 (study INCB 54329-101; NCT02431260) and INCB057643 (study INCB 57643-101; NCT02711137). PATIENTS AND
methodsPatients (≥18 years) with advanced malignancies, ≥1 prior therapy, and adequate organ functions received oral INCB054329 (monotherapy) or INCB057643 (monotherapy or in combination with standard-of-care) in 21-day cycles (or 28-day cycles depending on standard-of-care combination). Primary endpoints were safety and tolerability.
resultsSixty-nine and 134 patients received INCB054329 and INCB057643, respectively. Study INCB 54329-101 has been completed; INCB 57643-101 is currently active, but not recruiting (no patients were receiving treatment as of January 8, 2019). Terminal elimination half-life was shorter for INCB054329 versus INCB057643 (mean [SD], 2.24 [2.03] vs. 11.1 [8.27] hours). INCB054329 demonstrated higher interpatient variability in oral clearance versus INCB057643 (CV%, 142% vs. 45.5%). Most common (>20%) any-grade treatment-related adverse events were similar for both drugs (INCB054329; INCB057643): nausea (35%; 30%), thrombocytopenia (33%; 32%), fatigue (29%; 30%), decreased appetite (26%; 22%). Two confirmed complete responses and 4 confirmed partial responses with INCB057643 were reported as best responses.
conclusionsINCB057643 exhibited a more favorable PK profile versus INCB054329; exposure-dependent thrombocytopenia was observed with both drugs which limited the target inhibition that could be safely maintained. Further efforts are required to identify patient populations that can benefit most, and an optimal dosing scheme to maximize therapeutic index.
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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.