دورية أكاديمية
Safety, Efficacy, and Biological Data of T-Cell-Enabling Oncolytic Adenovirus TILT-123 in Advanced Solid Cancers from the TUNIMO Monotherapy Phase I Trial.
| العنوان: | Safety, Efficacy, and Biological Data of T-Cell-Enabling Oncolytic Adenovirus TILT-123 in Advanced Solid Cancers from the TUNIMO Monotherapy Phase I Trial. |
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| المؤلفون: | Pakola SA; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland., Peltola KJ; Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland., Clubb JHA; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.; TILT Biotherapeutics Ltd., Helsinki, Finland., Jirovec E; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland., Haybout L; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.; TILT Biotherapeutics Ltd., Helsinki, Finland., Kudling TV; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland., Alanko T; Docrates Cancer Center, Helsinki, Finland., Korpisaari R; Docrates Cancer Center, Helsinki, Finland., Juteau S; Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Jaakkola M; Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland., Sormunen J; Docrates Cancer Center, Helsinki, Finland., Kemppainen J; Docrates Cancer Center, Helsinki, Finland., Hemmes A; Digital Microscopy and Molecular Pathology Unit, Institute for Molecular Medicine Finland, Helsinki, Finland., Pellinen T; Digital Microscopy and Molecular Pathology Unit, Institute for Molecular Medicine Finland, Helsinki, Finland., van der Heijden M; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland., Quixabeira DCA; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.; TILT Biotherapeutics Ltd., Helsinki, Finland., Kistler C; TILT Biotherapeutics Ltd., Helsinki, Finland., Sorsa S; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.; TILT Biotherapeutics Ltd., Helsinki, Finland., Havunen R; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.; TILT Biotherapeutics Ltd., Helsinki, Finland., Santos JM; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.; TILT Biotherapeutics Ltd., Helsinki, Finland., Cervera-Carrascon V; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.; TILT Biotherapeutics Ltd., Helsinki, Finland., Hemminki A; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.; Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.; TILT Biotherapeutics Ltd., Helsinki, Finland. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Sep 03; Vol. 30 (17), pp. 3715-3725. |
| نوع المنشور: | Journal Article; Clinical Trial, Phase I; Multicenter Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : American Association for Cancer Research, c1995- |
| مواضيع طبية MeSH: | Neoplasms*/therapy , Neoplasms*/pathology , Oncolytic Viruses*/genetics , Oncolytic Virotherapy*/methods , Oncolytic Virotherapy*/adverse effects , T-Lymphocytes*/immunology , Adenoviridae*/genetics, Humans ; Female ; Middle Aged ; Male ; Aged ; Adult ; Treatment Outcome ; Interleukin-2/administration & dosage ; Interleukin-2/adverse effects |
| مستخلص: | Purpose: TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with TNFa and IL2, designed to induce T-cell infiltration and cytotoxicity in solid tumors. Patients and Methods: TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose-escalation trial designed to assess the safety of TILT-123 in advanced solid cancers refractory to standard therapy. Patients received intravenous and intratumoral TILT-123. The primary endpoint was safety by adverse events (AE), laboratory values, vital signs, and electrocardiograms. Secondary endpoints included tumor response, pharmacokinetics, and predictive biomarkers. Results: Twenty patients were enrolled, with a median age of 58 years. Most prevalent cancer types included sarcomas (35%), melanomas (15%) and ovarian cancers (15%). No dose-limiting toxicities were observed. The most frequent treatment-related AEs included fever (16.7%), chills (13.0%), and fatigue (9.3%). Ten patients were evaluable for response on day 78 with RECIST 1.1, iRECIST or PET-based evaluation. The disease control rate by PET was 6/10 (60% of evaluable patients) and 2/10 by RECIST 1.1 and iRECIST(20%of evaluable patients). Tumor size reductions occurred in both injected and non-injected lesions. TILT-123 was detected in injected and non-injected tumors, and virus was observed in blood after intravenous and intratumoral injections. Treatment resulted in reduction of lymphocytes in blood, with concurrent lymphocyte increases in tumors, findings compatible with trafficking. Conclusions: TILT-123 was safe and able to produce antitumor effects in local and distant lesions in heavily pre-treated patients. Good tolerability of TILT-123 facilitates combination studies, several of which are ongoing (NCT04217473, NCT05271318, NCT05222932, and NCT06125197). See related commentary by Silva-Pilipich and Smerdou, p. 3649. (©2024 The Authors; Published by the American Association for Cancer Research.) |
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| معلومات مُعتمدة: | Helsinki University Hospital Research funds; Cancer Foundation Finland; Jane and Aatos Erkko Foundation; Red Cross Blood Service; Sigrid Juselius Finland; TILT Biotherapeutics Oy; European Commision |
| المشرفين على المادة: | 0 (Interleukin-2) |
| تواريخ الأحداث: | Date Created: 20240328 Date Completed: 20240903 Latest Revision: 20240905 |
| رمز التحديث: | 20240905 |
| مُعرف محوري في PubMed: | PMC11369615 |
| DOI: | 10.1158/1078-0432.CCR-23-3874 |
| PMID: | 38546220 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-23-3874 |