Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors

Summary

The goal of this clinical trial is to learn if intratumoral administration of DNX-2401 works to treat recurrent and refractory high grade brain tumors in children and young adults. It will also learn about the safety of DNX-2401. The main questions it aims to answer are: * Does a single intratumoral administration of DNX-2401 elicit tumor response and improve survival? * Is a single intratumoral administration of DNX-2401 safe and well tolerated? Participants will: * Undergo surgery for tumor biopsy followed by a single intratumoral administration of DNX-2401 * Visit the clinic periodically for checkups and tests

Timeline

Start

2026-05-12

Primary completion

2029-05

Completion

2029-05

Publications

• Background Byer L, Kline CN, Coleman C, Allen IE, Whitaker E, Mueller S. A systematic review and meta-analysis of outcomes in pediatric, recurrent ependymoma. J Neurooncol. 2019 Sep;144(3):445-452. doi: 10.1007/s11060-019-03255-3. Epub 2019 Sep 9.
• Background Kline C, Felton E, Allen IE, Tahir P, Mueller S. Survival outcomes in pediatric recurrent high-grade glioma: results of a 20-year systematic review and meta-analysis. J Neurooncol. 2018 Mar;137(1):103-110. doi: 10.1007/s11060-017-2701-8. Epub 2017 Dec 4.
• Background Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.
• Background Gallego Perez-Larraya J, Garcia-Moure M, Labiano S, Patino-Garcia A, Dobbs J, Gonzalez-Huarriz M, Zalacain M, Marrodan L, Martinez-Velez N, Puigdelloses M, Laspidea V, Astigarraga I, Lopez-Ibor B, Cruz O, Oscoz Lizarbe M, Hervas-Stubbs S, Alkorta-Aranburu G, Tamayo I, Tavira B, Hernandez-Alcoceba R, Jones C, Dharmadhikari G, Ruiz-Moreno C, Stunnenberg H, Hulleman E, van der Lugt J, Idoate MA, Diez-Valle R, Esparragosa Vazquez I, Villalba M, de Andrea C, Nunez-Cordoba JM, Ewald B, Robbins J, Fueyo J, Gomez-Manzano C, Lang FF, Tejada S, Alonso MM. Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma. N Engl J Med. 2022 Jun 30;386(26):2471-2481. doi: 10.1056/NEJMoa2202028.
• Background Garcia-Moure M, Gonzalez-Huarriz M, Labiano S, Guruceaga E, Bandres E, Zalacain M, Marrodan L, de Andrea C, Villalba M, Martinez-Velez N, Laspidea V, Puigdelloses M, Gallego Perez-Larraya J, Inigo-Marco I, Stripecke R, Chan JA, Raabe EH, Kool M, Gomez-Manzano C, Fueyo J, Patino-Garcia A, Alonso MM. Delta-24-RGD, an Oncolytic Adenovirus, Increases Survival and Promotes Proinflammatory Immune Landscape Remodeling in Models of AT/RT and CNS-PNET. Clin Cancer Res. 2021 Mar 15;27(6):1807-1820. doi: 10.1158/1078-0432.CCR-20-3313. Epub 2020 Dec 29.
• Background Martinez-Velez N, Marigil M, Garcia-Moure M, Gonzalez-Huarriz M, Aristu JJ, Ramos-Garcia LI, Tejada S, Diez-Valle R, Patino-Garcia A, Becher OJ, Gomez-Manzano C, Fueyo J, Alonso MM. Delta-24-RGD combined with radiotherapy exerts a potent antitumor effect in diffuse intrinsic pontine glioma and pediatric high grade glioma models. Acta Neuropathol Commun. 2019 Apr 29;7(1):64. doi: 10.1186/s40478-019-0714-6.
• Background Martinez-Velez N, Garcia-Moure M, Marigil M, Gonzalez-Huarriz M, Puigdelloses M, Gallego Perez-Larraya J, Zalacain M, Marrodan L, Varela-Guruceaga M, Laspidea V, Aristu JJ, Ramos LI, Tejada-Solis S, Diez-Valle R, Jones C, Mackay A, Martinez-Climent JA, Garcia-Barchino MJ, Raabe E, Monje M, Becher OJ, Junier MP, El-Habr EA, Chneiweiss H, Aldave G, Jiang H, Fueyo J, Patino-Garcia A, Gomez-Manzano C, Alonso MM. The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models. Nat Commun. 2019 May 28;10(1):2235. doi: 10.1038/s41467-019-10043-0.
• Background Nassiri F, Patil V, Yefet LS, Singh O, Liu J, Dang RMA, Yamaguchi TN, Daras M, Cloughesy TF, Colman H, Kumthekar PU, Chen CC, Aiken R, Groves MD, Ong SS, Ramakrishna R, Vogelbaum MA, Khagi S, Kaley T, Melear JM, Peereboom DM, Rodriguez A, Yankelevich M, Nair SG, Puduvalli VK, Aldape K, Gao A, Lopez-Janeiro A, de Andrea CE, Alonso MM, Boutros P, Robbins J, Mason WP, Sonabend AM, Stupp R, Fueyo J, Gomez-Manzano C, Lang FF, Zadeh G. Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial. Nat Med. 2023 Jun;29(6):1370-1378. doi: 10.1038/s41591-023-02347-y. Epub 2023 May 15.
• Background Lang FF, Conrad C, Gomez-Manzano C, Yung WKA, Sawaya R, Weinberg JS, Prabhu SS, Rao G, Fuller GN, Aldape KD, Gumin J, Vence LM, Wistuba I, Rodriguez-Canales J, Villalobos PA, Dirven CMF, Tejada S, Valle RD, Alonso MM, Ewald B, Peterkin JJ, Tufaro F, Fueyo J. Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma. J Clin Oncol. 2018 May 10;36(14):1419-1427. doi: 10.1200/JCO.2017.75.8219. Epub 2018 Feb 12.
• Background Fueyo J, Alemany R, Gomez-Manzano C, Fuller GN, Khan A, Conrad CA, Liu TJ, Jiang H, Lemoine MG, Suzuki K, Sawaya R, Curiel DT, Yung WK, Lang FF. Preclinical characterization of the antiglioma activity of a tropism-enhanced adenovirus targeted to the retinoblastoma pathway. J Natl Cancer Inst. 2003 May 7;95(9):652-60. doi: 10.1093/jnci/95.9.652.
• Background Jiang H, Clise-Dwyer K, Ruisaard KE, Fan X, Tian W, Gumin J, Lamfers ML, Kleijn A, Lang FF, Yung WK, Vence LM, Gomez-Manzano C, Fueyo J. Delta-24-RGD oncolytic adenovirus elicits anti-glioma immunity in an immunocompetent mouse model. PLoS One. 2014 May 14;9(5):e97407. doi: 10.1371/journal.pone.0097407. eCollection 2014.
• Background Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231-1251. doi: 10.1093/neuonc/noab106.
• Background Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019. Neuro Oncol. 2022 Oct 5;24(Suppl 5):v1-v95. doi: 10.1093/neuonc/noac202.
• Background Cohen AR. Brain Tumors in Children. N Engl J Med. 2022 May 19;386(20):1922-1931. doi: 10.1056/NEJMra2116344. No abstract available.

Drugs

Indications