Assessing the safety, tolerability and efficacy of PLGA-based immunomodulatory nanoparticles in patients with advanced NY-ESO-1-positive cancers: a first-in-human phase I open-label dose-escalation study protocol.

Autor:	Creemers JHA; Department of Tumor Immunology, Radboudumc, Nijmegen, The Netherlands.; Oncode Institute, Nijmegen, The Netherlands., Pawlitzky I; CATO SMS, Amsterdam, The Netherlands., Grosios K; oncoKnow, Amsterdam, The Netherlands., Gileadi U; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK., Middleton MR; Department of Oncology, University of Oxford, Oxford, Oxfordshire, UK., Gerritsen WR; Department of Medical Oncology, Radboudumc, Nijmegen, The Netherlands., Mehra N; Department of Medical Oncology, Radboudumc, Nijmegen, The Netherlands., Rivoltini L; Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Lombardia, Italy., Walters I; iOx Therapeutics, London, UK., Figdor CG; Department of Tumor Immunology, Radboudumc, Nijmegen, The Netherlands.; Oncode Institute, Nijmegen, The Netherlands., Ottevanger PB; Department of Medical Oncology, Radboudumc, Nijmegen, The Netherlands., de Vries IJM; Department of Tumor Immunology, Radboudumc, Nijmegen, The Netherlands Jolanda.devries@radboudumc.nl.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2021 Nov 30; Vol. 11 (11), pp. e050725. Date of Electronic Publication: 2021 Nov 30.
DOI:	10.1136/bmjopen-2021-050725
Abstrakt:	Introduction: The undiminished need for more effective cancer treatments stimulates the development of novel cancer immunotherapy candidates. The archetypical cancer immunotherapy would induce robust, targeted and long-lasting immune responses while simultaneously circumventing immunosuppression in the tumour microenvironment. For this purpose, we developed a novel immunomodulatory nanomedicine: PRECIOUS-01. As a PLGA-based nanocarrier, PRECIOUS-01 encapsulates a tumour antigen (NY-ESO-1) and an invariant natural killer T cell activator to target and augment specific antitumour immune responses in patients with NY-ESO-1-expressing advanced cancers. Methods and Analysis: This open-label, first-in-human, phase I dose-escalation trial investigates the safety, tolerability and immune-modulatory activity of increasing doses of PRECIOUS-01 administered intravenously in subjects with advanced NY-ESO-1-expressing solid tumours. A total of 15 subjects will receive three intravenous infusions of PRECIOUS-01 at a 3-weekly interval in three dose-finding cohorts. The trial follows a 3+3 design for the dose-escalation steps to establish a maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D). Depending on the toxicity, the two highest dosing cohorts will be extended to delineate the immune-related parameters as a readout for pharmacodynamics. Subjects will be monitored for safety and the occurrence of dose-limiting toxicities. If the MTD is not reached in the planned dose-escalation cohorts, the RP2D will be based on the observed safety and immune-modulatory activity as a pharmacodynamic parameter supporting the RP2D. The preliminary efficacy will be evaluated as an exploratory endpoint using the best overall response rate, according to Response Evaluation Criteria in Solid Tumors V.1.1. Ethics and Dissemination: The Dutch competent authority (CCMO) reviewed the trial application and the medical research ethics committee (CMO Arnhem-Nijmegen) approved the trial under registration number NL72876.000.20. The results will be disseminated via (inter)national conferences and submitted for publication to a peer-reviewed journal. Trial Registration Number: NCT04751786. Competing Interests: Competing interests: IW is an employee of iOx Therapeutics and has stock ownership. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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