Academic Journal
First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors
| العنوان: | First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors |
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| المؤلفون: | Davis, Elizabeth J, Martín Liberal, Juan Jesús, Kristeleit, Rebecca S, Cho, Daniel, Blagden, Sarah P, Berthold, Dominik, Vieito Villar, Maria |
| المساهمون: | Institut Català de la Salut, Davis EJ Vanderbilt University Medical Center, Nashville, Tennessee, USA. Martin-Liberal J, Vieito M Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Kristeleit R Research Department of Oncology, University College London, London, UK. Cho DC Perlmutter Cancer Center, NYU Langone Health, NYU Grossman School of Medicine, New York, USA. Blagden SP Department of Oncology, University of Oxford, Oxford, UK. Berthold D Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | BMJ |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Càncer - Tractament, Avaluació de resultats (Assistència sanitària), Medicaments antineoplàstics - Ús terapèutic, DISEASES::Neoplasms, Other subheadings::Other subheadings::Other subheadings::/drug therapy, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome, CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents, ENFERMEDADES::neoplasias, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos |
| الوصف: | Inmunomodulación; Linfocitos T; Microambiente tumoral ; Immunomodulació; Limfòcits T; Microambient tumoral ; Immunomodulation; T-Lymphocytes; Tumor microenvironment ; Background OX40 is a costimulatory receptor upregulated on antigen-activated T cells and constitutively expressed on regulatory T cells (Tregs). INCAGN01949, a fully human immunoglobulin G1κ anti-OX40 agonist monoclonal antibody, was designed to promote tumor-specific immunity by effector T-cell activation and Fcγ receptor-mediated Treg depletion. This first-in-human study was conducted to determine the safety, tolerability, and preliminary efficacy of INCAGN01949. Methods Phase I/II, open-label, non-randomized, dose-escalation and dose-expansion study conducted in patients with advanced or metastatic solid tumors. Patients received INCAGN01949 monotherapy (7–1400 mg) in 14-day cycles while deriving benefit. Safety measures, clinical activity, pharmacokinetics, and pharmacodynamic effects were assessed and summarized with descriptive statistics. Results Eighty-seven patients were enrolled; most common tumor types were colorectal (17.2%), ovarian (8.0%), and non-small cell lung (6.9%) cancers. Patients received a median three (range 1–9) prior therapies, including immunotherapy in 24 patients (27.6%). Maximum tolerated dose was not reached; one patient (1.1%) receiving 350 mg dose reported dose-limiting toxicity of grade 3 colitis. Treatment-related adverse events were reported in 45 patients (51.7%), with fatigue (16 (18.4%)), rash (6 (6.9%)), and diarrhea (6 (6.9%)) being most frequent. One patient (1.1%) with metastatic gallbladder cancer achieved a partial response (duration of 6.3 months), and 23 patients (26.4%) achieved stable disease (lasting >6 months in one patient). OX40 receptor occupancy was maintained over 90% among all patients receiving doses of ≥200 mg, while no treatment-emergent antidrug antibodies were detected across all dose levels. Pharmacodynamic results demonstrated that treatment with INCAGN01949 did not enhance ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| ردمك: | 978-0-00-877526-1 0-00-877526-5 |
| تدمد: | 2051-1426 |
| Relation: | Journal for ImmunoTherapy of Cancer;10(10); http://dx.doi.org/10.1136/jitc-2021-004235; Davis EJ, Martin-Liberal J, Kristeleit R, Cho DC, Blagden SP, Berthold D, et al. First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors. J Immunother Cancer. 2022 Oct;10(10):e004235.; https://hdl.handle.net/11351/8540; 000877526500002 |
| DOI: | 10.1136/jitc-2021-004235 |
| الاتاحة: | https://hdl.handle.net/11351/8540 https://doi.org/10.1136/jitc-2021-004235 |
| Rights: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.C81F946C |
| قاعدة البيانات: | BASE |
Full Text Finder | ردمك: | 9780008775261 0008775265 |
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| تدمد: | 20511426 |
| DOI: | 10.1136/jitc-2021-004235 |