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, Hyung Joon Yim, Kwan Soo 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

5 Citations (Scopus)

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
JournalOncoImmunology
DOIs
Publication statusPublished - 2019 Jan 1

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Vaccinia
Immunotherapy
Hepatocellular Carcinoma
Survival
Tumor-Associated Carbohydrate Antigens
Oncolytic Viruses
Safety
Vaccinia virus
Therapeutics
Granulocyte-Macrophage Colony-Stimulating Factor
Intravenous Infusions
Hypotension
Immunity
Neoplasms
Fever
sorafenib
T-Lymphocytes
Antigens
Injections

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure : a randomized multicenter Phase IIb trial (TRAVERSE). / Moehler, M.; Heo, J.; Lee, H. C.; Tak, W. Y.; Chao, Y.; Paik, S. W.; Yim, Hyung Joon; Byun, Kwan Soo; 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.

In: OncoImmunology, 01.01.2019.

Research output: Contribution to journalArticle

Moehler, M, Heo, J, Lee, HC, Tak, WY, Chao, Y, Paik, SW, Yim, HJ, Byun, KS, Baron, A, Ungerechts, G, Jonker, D, Ruo, L, Cho, M, Kaubisch, A, Wege, H, Merle, P, Ebert, O, Habersetzer, F, Blanc, JF, Rosmorduc, O, Lencioni, R, Patt, R, Leen, AM, Foerster, F, Homerin, M, Stojkowitz, N, Lusky, M, Limacher, JM, Hennequi, M, Gaspar, N, McFadden, B, De Silva, N, Shen, D, Pelusio, A, Kirn, DH, Breitbach, CJ & Burke, JM 2019, 'Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE)', OncoImmunology. https://doi.org/10.1080/2162402X.2019.1615817
Moehler, M. ; Heo, J. ; Lee, H. C. ; Tak, W. Y. ; Chao, Y. ; Paik, S. W. ; Yim, Hyung Joon ; Byun, Kwan Soo ; 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. / Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure : a randomized multicenter Phase IIb trial (TRAVERSE). In: OncoImmunology. 2019.
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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-na{\"i}ve 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.",
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T1 - Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure

T2 - a randomized multicenter Phase IIb trial (TRAVERSE)

AU - Moehler, M.

AU - Heo, J.

AU - Lee, H. C.

AU - Tak, W. Y.

AU - Chao, Y.

AU - Paik, S. W.

AU - Yim, Hyung Joon

AU - Byun, Kwan Soo

AU - Baron, A.

AU - Ungerechts, G.

AU - Jonker, D.

AU - Ruo, L.

AU - Cho, M.

AU - Kaubisch, A.

AU - Wege, H.

AU - Merle, P.

AU - Ebert, O.

AU - Habersetzer, F.

AU - Blanc, J. F.

AU - Rosmorduc, Olivier

AU - Lencioni, R.

AU - Patt, R.

AU - Leen, A. M.

AU - Foerster, F.

AU - Homerin, M.

AU - Stojkowitz, N.

AU - Lusky, M.

AU - Limacher, J. M.

AU - Hennequi, M.

AU - Gaspar, N.

AU - McFadden, B.

AU - De Silva, N.

AU - Shen, D.

AU - Pelusio, A.

AU - Kirn, D. H.

AU - Breitbach, C. J.

AU - Burke, J. M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Hepatocellular carcinoma

KW - oncolytic immunotherapy

KW - oncolytic vaccinia

KW - Pexa-Vec

KW - sorafenib

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