학술논문
Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE)
Document Type
article
Author
M. Moehler; J. Heo; H.C. Lee; W.Y. Tak; Y. Chao; S.W. Paik; H.J. Yim; K.S. Byun; A. Baron; G. Ungerechts; D. Jonker; L. Ruo; M. Cho; A. Kaubisch; H. Wege; P. Merle; O. Ebert; F. Habersetzer; J.F. Blanc; Olivier Rosmorduc; R. Lencioni; R. Patt; A.M. Leen; F. Foerster; M. Homerin; N. Stojkowitz; M. Lusky; J.M. Limacher; M. Hennequi; N. Gaspar; B. McFadden; N. De Silva; D. Shen; A. Pelusio; D.H. Kirn; C.J. Breitbach; J.M. Burke
Source
OncoImmunology, Vol 8, Iss 8 (2019)
Subject
Language
English
ISSN
2162-402X
2162402X
2162402X
Abstract
Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naïve hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE). 129 patients were randomly assigned 2:1 to Pexa-Vec plus BSC vs. BSC alone. Pexa-Vec was given as a single intravenous (IV) infusion followed by up to 5 IT injections. The primary endpoint was OS. Secondary endpoints included overall response rate (RR), time to progression (TTP) and safety. A high drop-out rate in the control arm (63%) confounded assessment of response-based endpoints. Median OS (ITT) for Pexa-Vec plus BSC vs. BSC alone was 4.2 and 4.4 months, respectively (HR, 1.19, 95% CI: 0.78–1.80; p = .428). There was no difference between the two treatment arms in RR or TTP. Pexa-Vec was generally well-tolerated. The most frequent Grade 3 included pyrexia (8%) and hypotension (8%). Induction of immune responses to vaccinia antigens and HCC associated antigens were observed. Despite a tolerable safety profile and induction of T cell responses, Pexa-Vec did not improve OS as second-line therapy after sorafenib failure. The true potential of oncolytic viruses may lie in the treatment of patients with earlier disease stages which should be addressed in future studies. ClinicalTrials.gov: NCT01387555