1 First Department of Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
2 College of Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
3 Asan Medical Center, University of Ulsan College of Medicine, Ulsan, Republic ofKorea.
4 School of Medicine, Kyungpook National University Medical Center, Daegu, Republic of Korea.
5 Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
6 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
7 Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Republic of Korea.
8 Department of Internal Medicine, Korea UniversityCollege of Medicine, Seoul, Republic of Korea.
9 Department of Medicine, California Pacific Medical Center, San Francisco, CA, USA.
10 Department of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Heidelberg, Germany.
11 The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
12 Department of Surgery, Juravinski Hospital and Cancer Centre, McMaster University, Hamilton, Canada.
13 Department of Internal Medicine, Pusan National University Yangsan Hospital, Busan, Republic of Korea.
14 Department of Medicine, Montefiore Medical Center, New York, NY, USA.
15 Department of Medicine, Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
16 Hepatology Unit, Croix-Rousse Hospital, Lyon, France.
17 Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University, Munich, Germany.
18 Pôle Hépato-Digestif, Hôpitaux Universitaires de Strasbourg, INSERM 1110, IHU de Strasbourg and Université de Strasbourg, Strasbourg, France.
19 Hepato-Gastroenterology and Digestive Oncology Department, CHU Bordeaux, Bordeaux, France.
20 Sorbonne Université, AP-HP, Hôpital Paul Brousse, Villejuif, France.
21 Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
22 Rad-MD, New York, NY, USA.
23 Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
24 Medical Affairs, Transgene S.A., Illkirch-Graffenstaden, France.
25 Clinical Operations, Transgene S.A., 400 Bd Gonthier d'Andernach, Parc d'Innovation, 67405 Illkirch-Graffenstaden, France.
26 Program Management, Transgene S.A., 400 Bd Gonthier d'Andernach, Parc d'Innovation, 67405 Illkirch-Graffenstaden, France.
27 Medical Affairs, Transgene S.A., 400 Bd Gonthier d'Andernach, Parc d'Innovation, 67405 Illkirch-Graffenstaden, France.
28 Biostatistics, Transgene S.A., 400 Bd Gonthier d'Andernach, Parc d'Innovation, 67405 Illkirch-Graffenstaden, France.
29 Clinical Assays, SillaJen Inc., San Francisco, CA, USA.
30 Analytical Development and Quality Control, SillaJen Inc., San Francisco, CA, USA.
31 Clinical, SillaJen Inc., San Francisco, CA, USA.
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.