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

M Moehler (1) , J Heo (2) , H Lee (3) , W Tak (4) , Y Chao (5) , S Paik (6) , H Yim , K Byun (7) , A Baron (8) , G Ungerechts (9) , D Jonker (10) , L Ruo (11) , M Cho (12) , A Kaubisch (13) , H Wege (14) , P Merle (15) , O Ebert (16) , Francois Habersetzer (17, 18, 19) , J Blanc (20) , O Rosmorduc (21, 22) , R Lencioni (23) , R Patt , A Leen (24) , F Foerster (1) , M Homerin (25) , N Stojkowitz (25) , M Lusky (25) , J Limacher (25) , M Hennequi (25) , N Gaspar , B Mcfadden , N de Silva , D Shen , A Pelusio , D Kirn , C Breitbach , J Burke

1 University Medical Center of the Johannes Gutenberg-University Mainz
2 Pusan National University Hospital
3 University of Ulsan
4 KNU - Kyungpook National University [Daegu]
5 Taipei Veterans General Hospital [Taiwan]
6 Samsung Medical Center Sungkyunkwan University School of Medicine
7 Korea University [Seoul]
8 California Pacific Medical Center Research Institute
9 Heidelberg University Hospital [Heidelberg]
10 University of Ottawa [Ottawa]
11 McMaster University [Hamilton, Ontario]
12 PNU - Pusan National University
13 Montefiore Medical Center [Bronx, New York]
14 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
15 Hôpital de la Croix-Rousse [CHU - HCL]
16 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
17 IVH - Institut de Recherche sur les Maladies Virales et Hépatiques
18 HUS - Les Hôpitaux Universitaires de Strasbourg
19 IHU Strasbourg - L'Institut hospitalo-universitaire de Strasbourg
20 CHU Bordeaux
21 Hôpital Paul Brousse
22 SU - Sorbonne Université
23 UMMSM - University of Miami Leonard M. Miller School of Medicine
24 BCM - Baylor College of Medicine
25 Transgene SA [Illkirch]

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-naive 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.

Mots clés: Hepatocellular carcinoma; Pexa-Vec; oncolytic immunotherapy; oncolytic vaccinia; sorafenib

Domaines: Médecine humaine et pathologie

M Moehler, J Heo, H Lee, W Tak, Y Chao, et al.. Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE). Oncoimmunology, 2019, 8 (8), ⟨10.1080/2162402X.2019.1615817⟩. ⟨hal-02390247⟩