Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE). (3rd August 2019)

• Record Type: Journal Article
• Authors: 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.; Rosmorduc, Olivier; Lencioni, R.; Patt, R.; Leen, A.M.; Foerster, F.; Homerin, M.; Stojkowitz, N.; Lusky, M.; Limacher, J.M.; Hennequi, M.; Gaspar, N.; McFadden, B.; De Silva, N.; Shen, D.; Pelusio, A.; Kirn, D.H.; Breitbach, C.J.; Burke, J.M.;
• Is Part Of: Oncoimmunology. Volume 8:Number 8(2019)
• Publication Date: 2019-08-03
• Subjects: Hepatocellular carcinoma -- Pexa-Vec -- sorafenib -- oncolytic immunotherapy -- oncolytic vaccinia; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2019.1615817
• Languages: English
• ISSNs: 2162-402X

Abstract

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