Neural stem cell delivery of an oncolytic adenovirus in newly diagnosed malignant glioma: a first-in-human, phase 1, dose-escalation trial.

BACKGROUND

Malignant glioma is the most common and lethal primary brain tumour, with dismal survival rates and no effective treatment. We examined the safety and activity of NSC-CRAd-S-pk7, an engineered oncolytic adenovirus delivered by neural stem cells (NSCs), in patients with newly diagnosed high-grade glioma.

METHODS

This was a first-in-human, open-label, phase 1, dose-escalation trial done to determine the maximal tolerated dose of NSC-CRAd-S-pk7, following a 3 + 3 design. Patients with newly diagnosed, histologically confirmed, high-grade gliomas (WHO grade III or IV) were recruited. After neurosurgical resection, NSC-CRAd-S-pk7 was injected into the walls of the resection cavity. The first patient cohort received a dose starting at 6·25 × 10

FINDINGS

Between April 24, 2017, and Nov 13, 2019, 12 patients with newly diagnosed, malignant gliomas were recruited and included in the safety analysis. Histopathological evaluation identified 11 (92%) of 12 patients with glioblastoma and one (8%) of 12 patients with anaplastic astrocytoma. The median follow-up was 18 months (IQR 14-22). One patient receiving 1·50 × 10

INTERPRETATION

NSC-CRAd-S-pk7 treatment was feasible and safe. Our immunological and histopathological findings support continued investigation of NSC-CRAd-S-pk7 in a phase 2/3 clinical trial.

FUNDING

US National Institutes of Health.

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests JP reports grants from The Ivy Foundation, during the conduct of this study. CDH reports salary payments from Southern Research, outside the submitted work. RVL reports honoraria from Novocure for advisory roles, EBSCO Publishing and Medlink Neurology for medical editing, ECRI for reviewing medical content, and the American Physician Institute for creating and presenting board review continuing medical education material, outside the submitted work. RS reports non-financial support from CarThera, and personal fees from Celularity, CranioVation, TriAct, Hemispherian, Northwest Biotherapeutics, GT Medical Technologies, Insightec, and ZaiLab, outside the submitted work. DTC, KSA, and MSL have an issued patent that is related to the study (US10238699 and US10709745). KSA was the CSO and Director of TheraBiologics (company in process of being dissolved) during the conduct of this study; she neither has assets nor receives financial benefit from the company. MSL reports grants from the National Institutes of Health, during the conduct of this study. All other authors declare no competing interests.