Table 5 Several representative clinical trials of non-cell based vaccines and oncolytic virus (OVs) based immunotherapy in HCC

Greten et al. (2010)

GV1001: a telomerase derived peptide vaccine

• A phase 2 open-label trial; 4-week injections with GM-CSF + GV1001 vaccinations

• P:tumor response

• S:TTP, TTSP, PFS, OS, safety and immune responses

40 patients with advanced HCC

Status: terminated

Results: no relevant toxicity, median OS: 11.5 months, median PFS: 57 days, median TTP: 57 days, TTSP: 11.7 months

[155]

NCT00444782

Sawada et al. (2012)

GPC-3-derived peptide vaccine

• A phase 1 Trial

• P: safety

• S:TTP, OS, immune responses (measured by IFN-γ ELISPOT assay)

33 patients with advanced HCC

Status: terminated

Results: well-tolerated, 91% patients were successfully induced with CTLs-mediated responses, median OS: 9.0 months, median TTP: 3.4 months, GPC-3-specific CTL frequency after vaccination correlated with OS

[156]

UMIN-CTR000001395

Butterfield et al. (2003)

AFP peptide vaccine

• A pilot Phase 1 clinical trial

• In vivo studies testing AFP peptide- vaccine reactive T cells responses

6 patients with HCC

Status: terminated

Results: all of the patients generated T-cell responses to most or all of the peptides as measured by direct IFN –γ ELISPOT and MHC class I tetramer assays

[157]

Immunitor LLC et al. (2018)

An oral therapeutic vaccine: hepcortespenlisimut-L (Hepko-V5)

• A phase 3, randomized, placebo-controlled, double-blinded trial

• P:changes in serum AFP levels, tumor burden, OS

Estimated enrollment:120 patients with advanced HCC

Status: recruiting

Results: none

NCT02232490

Roswell Park Cancer Institute (2016)

Vaccine therapy in treating NY-ESO-1 expressing solid tumors

• A phase 1 clinical trial determines the safety of DC205-NY-ESO-1 vaccine

18 patients with NY-ESO-1 solid tumors, including HCC

Status: completed

Results: none

NCT01522820

Butterfield et al. (2013)

AFP+ GM-CSF Plasmid Prime and AFP Adenoviral vector Boost

• A phase 1/2 trial

• Testing immunization with AFP + GM CSF plasmid prime and AFP adenoviral vector

Actual enrollment:

2 patients with HCC

Status: terminated (Poor accrual and limited target patient population for future accrual, did not complete the Phase 1 portion of the trial.)

NCT00669136

Byeong et al. (2008)

JX-594

• A phase 1 clinical trial, assessment of intratumoral injection of JX-594 into primary or metastatic liver tumours

• P:safety, MTD

14 patients with primary or metastatic liver tumors

Status: terminated

Results: well-tolerated;

MTD was determined as 1 × 10⁹ pfu; 10 patients were radiographically evaluable for objective responses; responses in 3 HCC patients: 3 serum tumor markers PR (≥50% decrease); 1 response according to PET

[158] (NCT00629759)

Jeong Heo et al. (2013)

JX-594

• A Prospective, randomized clinical trial with high or low dose JX-594

• P: intrahepatic disease control rate

30 patients with unresectable liver tumors

Status: terminated

Results: 11/16 patients showed cytotoxicity against HCC; 31% anorexia in high dose group

RR: 4 PR, 10 SD by RECIST

[159] (NCT00554372)

Jennerex Biotherapeutics (2008–2011)

JX-594 (Pexa-Vec)

• A phase 2b randomized trial

• JX-594 plus best supportive care versus best supportive care in patients with advanced HCC who have failed Sorafenib treatment

129 patients with advanced HCC who have failed sorafenib

Status: completed

Results: none

(No results posted on ClinicalTrials.gov)

NCT01387555

SillaJen, Inc. (2015)

Vaccinia virus based immunotherapy (Pexa-Vec) + Sorafenib

• A multi-center, randomized, open-label, Phase 3 trial;

• Comparing Vaccinia Virus based Immunotherapy Plus Sorafenib vs Sorafenib alone

600 patients with advanced HCC

Status: recruiting

Results: none

NCT02562755