ArticleMolecular cancer therapeutics2023
First-in-human Study of AZD5153, A Small-molecule Inhibitor of Bromodomain Protein 4, in Patients with Relapsed/Refractory Malignant Solid Tumors and Lymphoma.
Article in Molecular cancer therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Senescence-directed nanotherapy ameliorates fibrosis and overcomes immune exclusion in cancer.Science (New York, N.Y.) · 2026Article
- Bridging BET bromodomain and immune checkpoint inhibitors through generative bioorganic frameworks for next-generation cancer immunotherapy.RSC medicinal chemistry · 2026Review
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- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Targeting DNA repair mechanisms in cancer therapy: the role of small molecule DNA repair inhibitors.NAR cancer · 2025Review
- Adverse drug reaction profiles of histone deacetylase inhibitors.Scientific reports · 2025Article
- Therapeutic Targeting of BET Proteins in Sarcoma.Molecular cancer therapeutics · 2025Review
- AZD5153 enhances the chemo-sensitivity of gemcitabine on pancreatic cancer cells in vitro and in vivo.Cancer cell international · 2025Article
- Combination of PSMA targeting alpha-emitting radioligand [Medical oncology (Northwood, London, England) · 2025Article
- Targeting MYC: Multidimensional regulation and therapeutic strategies in oncology.Genes & diseases · 2025Review
- Dual targeting of Aurora Kinase A and poly (ADP-ribose) polymerase as a therapeutic option for patients with ovarian cancer: preclinical evaluations.Journal of cancer research and clinical oncology · 2025Article
- Functional combinatorial precision medicine for predicting and optimizing soft tissue sarcoma treatments.NPJ precision oncology · 2025Article
- Effective therapeutic targeting of tumor lineage plasticity in neuroendocrine prostate cancer by BRD4 inhibitors.Acta pharmaceutica Sinica. B · 2025Article
- Bromodomain and extra-terminal proteins in solid tumors: regulators of immune microenvironment and emerging therapeutic targets.Frontiers in immunology · 2025Review
- 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
- Lipid metabolism-related gene signature predicts prognosis and unveils novel anti-tumor drugs in specific type of diffuse large B cell lymphoma.Molecular medicine (Cambridge, Mass.) · 2024Article
- Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance.NPJ precision oncology · 2024Review
- Targeting super-enhancer activity for colorectal cancer therapy.American journal of translational research · 2024Review
- The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells.NPJ precision oncology · 2022Article
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Authors and funding
17 authors at 6 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AZD5153, a reversible, bivalent inhibitor of the bromodomain and extraterminal family protein BRD4, has preclinical activity in multiple tumors. This first-in-human, phase I study investigated AZD5153 alone or with olaparib in patients with relapsed/refractory solid tumors or lymphoma. Adults with relapsed tumors intolerant of, or refractory to, prior therapies received escalating doses of oral AZD5153 once daily or twice daily continuously (21-day cycles), or AZD5153 once daily/twice daily continuously or intermittently plus olaparib 300 mg twice daily, until disease progression or unacceptable toxicity. Between June 30, 2017 and April 19, 2021, 34 patients received monotherapy and 15 received combination therapy. Dose-limiting toxicities were thrombocytopenia/platelet count decreased (n = 4/n = 2) and diarrhea (n = 1). The recommended phase II doses (RP2D) were AZD5153 30 mg once daily or 15 mg twice daily (monotherapy) and 10 mg once daily (intermittent schedule) with olaparib. With AZD5153 monotherapy, common treatment-emergent adverse events (TEAE) included fatigue (38.2%), thrombocytopenia, and diarrhea (each 32.4%); common grade ≥ 3 TEAEs were thrombocytopenia (14.7%) and anemia (8.8%). With the combination, common TEAEs included nausea (66.7%) and fatigue (53.3%); the most common grade ≥ 3 TEAE was thrombocytopenia (26.7%). AZD5153 had dose-dependent pharmacokinetics, with minimal accumulation, and demonstrated dose-dependent modulation of peripheral biomarkers, including upregulation of HEXIM1. One patient with metastatic pancreatic cancer receiving combination treatment had a partial response lasting 4.2 months. These results show AZD5153 was tolerable as monotherapy and in combination at the RP2Ds; common toxicities were fatigue, hematologic AEs, and gastrointestinal AEs. Strong evidence of peripheral target engagement was observed.
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