ArticleInvestigational new drugs2017
First-in-human study of the antibody DR5 agonist DS-8273a in patients with advanced solid tumors.
Article in Investigational new drugs, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed.
- Cytotoxic activity and safety characterization of IMV-M™, a MUC16 × DR5 bispecific antibody.Antibody therapeutics · 2026Article
- DR5 CAR-T cells target melanoma and suppress MDSCs with minimal toxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Advances in the study of death receptor 5.Frontiers in pharmacology · 2025Review
- Beyond ADCs: harnessing bispecific antibodies to directly induce apoptosis for targeted tumor eradication.Antibody therapeutics · 2024Review
- Agonist Antibodies for Cancer Immunotherapy: History, Hopes, and Challenges.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Targeting regulated cell death pathways in cancers for effective treatment: a comprehensive review.Frontiers in cell and developmental biology · 2024Review
- Counteracting Immunosenescence-Which Therapeutic Strategies Are Promising?Biomolecules · 2023Review
- Exosomal delivery of TRAIL and miR‑335 for the treatment of hepatocellular carcinoma (Review).International journal of molecular medicine · 2023Review
- Eftozanermin alfa (ABBV-621) monotherapy in patients with previously treated solid tumors: findings of a phase 1, first-in-human study.Investigational new drugs · 2022Article
- Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?Cancers · 2022Review
- Subcellular Proteome Analysis Reveals Apoptotic Vulnerability of T-Cell Acute Lymphoblastic Leukemia.BioMed research international · 2022Article
- Activity and rational combinations of a novel, engineered chimeric, TRAIL-based ligand in diffuse large B-cell lymphoma.Frontiers in oncology · 2022Article
- The role of innate immune cells in the tumor microenvironment and research progress in anti-tumor therapy.Frontiers in immunology · 2022Review
- Myeloid-derived suppressor cells and the pathogenesis of human immunodeficiency virus infection.Open biology · 2021Review
- Therapeutics Targeting the Core Apoptotic Machinery.Cancers · 2021Review
- Article
- Granulocytes and Cells of Granulocyte Origin-The Relevant Players in Colorectal Cancer.International journal of molecular sciences · 2021Review
- Review
- Heightened JNK Activation and Reduced XIAP Levels Promote TRAIL and Sunitinib-Mediated Apoptosis in Colon Cancer Models.Cancers · 2019Article
- Cancer immunotherapy beyond immune checkpoint inhibitors.Journal of hematology & oncology · 2018Review
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background DR5 is a transmembrane receptor that transduces extracellular ligand-binding to activate apoptosis signaling cascades. This phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of a new monoclonal antibody potent DR5 agonist, DS-8273a, in subjects with advanced solid tumors. Methods The study comprised dose escalation and dose expansion cohorts. The dose escalation cohorts intended to determine the safety and to identify the maximum tolerated dose (MTD) or maximum administered dose (MAD) and to characterize the pharmacokinetics and pharmacodynamics by a conventional 3 + 3 design (starting at 2 mg/kg and escalating through 8, 16 and 24 mg/kg once every 3 weeks). In the dose expansion cohort, additional subjects were treated at the MAD for further evaluation of PK and safety. Results Thirty two subjects were enrolled and treated, 16 in the dose escalation cohorts and 16 in the dose expansion cohort. No subjects experienced a dose limiting toxicity (DLT). Treatment emergent adverse events were observed in 29 (91%) subjects, 14 (44%) of which were attributed to study-drug; all drug-related events were grade 1 and 2 in severity, and were mainly fatigue, nausea, vomiting and diarrhea. Measures of plasma exposure increased dose-proportionally and the mean terminal elimination half-life was 11 days. Blood samples available from a subset of patients treated at 24 mg/kg revealed declines in myeloid derived suppressor cells (MDSC) at 2 weeks. No objective responses were observed in any subjects. Conclusions DS-8273a was well tolerated and demonstrated linear pharmacokinetics. Decreases in MDSC were temporally associated with DS-8273a exposure. This agent could be studied further in combination with other agents, pending further proof-of-target-engagement.
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Registered trials
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