Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial

Author:

Galanis EvanthiaORCID,Dooley Katharine E.ORCID,Keith Anderson S.ORCID,Kurokawa Cheyne B.,Carrero Xiomara W.,Uhm Joon H.,Federspiel Mark J.,Leontovich Alexey A.,Aderca Ileana,Viker Kimberly B.,Hammack Julie E.,Marks Randolph S.,Robinson Steven I.,Johnson Derek R.,Kaufmann Timothy J.,Buckner Jan C.,Lachance Daniel H.,Burns Terry C.ORCID,Giannini CaterinaORCID,Raghunathan Aditya,Iankov Ianko D.,Parney Ian F.

Abstract

AbstractMeasles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was safety and toxicity: treatment was well tolerated with no dose-limiting toxicity being observed up to the maximum feasible dose (2×107 TCID50). Median OS, a secondary endpoint, was 11.6 mo and one year survival was 45.5% comparing favorably with contemporary controls. Other secondary endpoints included assessment of viremia, MV replication and shedding, humoral and cellular immune response to the injected virus. A 22 interferon stimulated gene (ISG) diagonal linear discriminate analysis (DLDA) classification algorithm in a post-hoc analysis was found to be inversely (R = −0.6, p = 0.04) correlated with viral replication and tumor microenvironment remodeling including proinflammatory changes and CD8 + T cell infiltration in post treatment samples. This data supports that oncolytic MV derivatives warrant further clinical investigation and that an ISG-based DLDA algorithm can provide the basis for treatment personalization.

Funder

U.S. Department of Health & Human Services | NIH | National Cancer Institute

The Ben & Catherine Ivy Foundation

Publisher

Springer Science and Business Media LLC

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