Targets of immunotherapy for hepatocellular carcinoma: An update

Table 7 Ongoing clinical trial for combination therapy for hepatocellular carcinoma

Immune checkpoint/vaccine therapy	Radiotherapy/other therapy	Phase	Study design	Status	Trial ID
Ipilimumab	Nivolumab	Phase I/II	To assess the effects of combination treatment with nivolumab and ipilimumab pre-operatively in HCC	Recruiting patients	NCT03682276
Nivolumab	Ipilimumab	Phase I	To compare the overall survival of nivolumab plus ipilimumab vs standard of care (sorafenib or lenvatinib) in patients with advanced HCC	Recruiting patients	NCT04039607
Nivolumab	Ipilimumab	Phase II	Nivolumab plus Ipilimumab as neoadjuvant therapy for HCC; To test efficacy, tumor shrinkage, and objective response rate	Recruiting patients	NCT03510871
Nivolumab	Ipilimumab	Phase II	Nivolumab with or without ipilimumab in treating patients with resectable liver cancer		NCT03222076
Nivolumab, ipilimumab	SBRT	Phase I	To determine the safety and tolerability of SBRT followed by nivolumab or ipilimumab in HCC	Active, not recruiting	NCT03203304
Pembrolizumab	Talimogene laherparepvec (genetically modified oncolytic viral therapy)	Phase Ib/II	Multicenter, open-label, basket trial; To evaluate the safety of talimogene laherparepvec injected intra-hepatically into liver tumors alone and in combination with systemic IV administration of pembrolizumab	Recruiting patients	NCT02509507; MK-3475-611/Keynote-611 (MASTERKEY-318)
Nivolumab	Pexa-Vec	Phase I/II	To evaluate the safety and efficacy in HCC	Active, not recruiting	NCT03071094
Modified vaccinia virus ankara vaccine expressing p53	Pembrolizumab	Phase I	To study the side effects of vaccine therapy and in treating patients with solid tumors with metastasis	Active, not recruiting	NCT02432963
GNOS-PV02 (personalized neoantigen DNA vaccine)	Plasma encoded IL-12 (INO-9012) pembrolizumab	Phase I/IIa	A single-arm, open-label, multi-site study of GNOS-PV02 and INO-9012 in combination with pembrolizumab (MK-3475) in histologically or cytologically confirmed HCC	Recruiting patients	NCT04251117
DNAJB1-PRKACA fusion kinase peptide vaccine	Nivolumab and Ipilimumab	Phase I	To study the safety and tolerability of administering a vaccine targeting the DNAJB1-PRKACA fusion kinase, in combination with nivolumab and ipilimumab in unresectable or metastatic fibrolamellar HCC	Recruiting patients	NCT04248569
Durvalumaband tremelimumab	Sorafenib	Phase III	To assess the efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab monotherapy vs sorafenib in the treatment of patients with no prior systemic therapy for unresectable HCC		NCT03298451
TremelimumabDurvalumab (MEDI4736)	Radiation therapy	Phase II	To test the combination therapy as a possible treatment for HCC or biliary tract cancer	Recruiting patients	NCT03482102
Nivolumab	Y90-radioembolization	Phase II	To evaluate the response rates of Y90 radioembolization in combination with nivolumab in HCC	Recruiting patients	NCT03033446
Ipilimumab	SBRT	Phase I	To find the highest tolerable dose of ipilimumab and SBRT in liver and lung cancer	Completed but no results posted	NCT02239900
Nivolumab	TACE	Phase II (IMMUTACE)	To evaluates the safety and the efficacy of nivolumab in combination with TACE in patients with multinodular, intermediate stage HCC as first line therapy	Active, not recruiting	NCT03572582
Pembrolizumab	TACE	Phase I/II (PETAL)	Open label, single arm, multi-centre study; To determine the safety and tolerability of pembrolizumab following TACE	Recruiting patients	NCT03397654
Durvalumab; Tremelimumab	TACE; RFA; Cryoablation	Phase II	To evaluate the 6-mo progression free survival with combination therapy in patients with HCC	Recruiting patients	NCT02821754
Immune Checkpoint Inhibitor	TACE; SBRT	Phase II; START-FIT	Sequential TACE and SBRT with immunotherapy	Recruiting patients	NCT03817736
Durvalumab	Tremelimumab	Phase II	To evaluate the safety, tolerability, antitumor activity, pharmacokinetics, pharmacodynamics, and immunogenicity of durvalumab or tremelimumab monotherapy, or durvalumab in combination with tremelimumab or bevacizumab in advanced HCC; Initial reports of concerns with safety and efficacy of the combination of durvalumab and tremelimumab in HCC	Active, not recruiting	NCT02519348

SBRT: Stereotactic body radiotherapy; TACE: Trans-arterial chemoembolization; HCC: Hepatocellular carcinoma; RFA: Radiofrequency ablation.