Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE)

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 RosmorducR. 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

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Article numbere1615817
JournalOncoImmunology
Volume8
Issue number8
DOIs
StatePublished - Jan 1 2019

Keywords

  • Hepatocellular carcinoma
  • Pexa-Vec
  • oncolytic immunotherapy
  • oncolytic vaccinia
  • sorafenib

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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    Moehler, M., Heo, J., Lee, H. C., Tak, W. Y., Chao, Y., Paik, S. W., Yim, H. J., Byun, K. S., Baron, A., Ungerechts, G., Jonker, D., Ruo, L., Cho, M., Kaubisch, A., Wege, H., Merle, P., Ebert, O., Habersetzer, F., Blanc, J. F., ... Burke, J. M. (2019). Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE). OncoImmunology, 8(8), [e1615817]. https://doi.org/10.1080/2162402X.2019.1615817