Table 2 Combination treatment of hepatocellular carcinoma (HCC) in clinical trials

 Atezolizumab plus Lenvatinib or Sorafenib

PD-L1 + VEGFRs, FGFRs, PDGFR α, RET, KIT and RAF

Advanced;

Second-line

III

OS

NCT04770896

2021

 SHR-1210 plus Apatinib

PD-1 + VEGFR-2

Advanced;

First-line

III

OS/PFS

NCT03764293

2019

 CS1003 plus Lenvatinib

PD-1 + VEGFRs, FGFRs, PDGFR α, RET and KIT

Advanced;

First-line

III

OS/PFS

NCT04194775

2019

 Durvalumab plus Bevacizumab

PD-L1 + VEGFA

High risk of recurrence;

Second-line

III

RFS

NCT03847428

2019

 Atezolizumab plus Bevacizumab

PD-L1 + VEGFA

Locally advanced or metastatic; First-line

III

OS/PFS

NCT03434379

2018

 Atezolizumab plus Cabozantinib

PD-L1 + VEGFR, MET, RET, KIT and AXL

Advanced;

First-line

III

OS/PFS

NCT03755791

2018

 Pembrolizumab plus Lenvatinib

PD-1 + VEGFRs, FGFRs, PDGFR α, RET and KIT

Advanced;

First-line

III

OS/PFS

NCT03713593

2018

 Nivolumab plus Sorafenib

PD-1 + VEGFRs, KIT, PDGFRs, and RAF

Locally Advanced or Metastatic; First-line

II

MTD/ORR

NCT03439891

2018

 Avelumab plus Regorafenib

PD-L1 + VEGFR1–3, PDGFR-β, FGFR1, KIT, RET and B-RAF

Advanced or metastatic

I/II

RP2D/ORR

NCT03475953

2018

 Nivolumab plus Cabozantinib

PD-1 + VEGFR, MET, RET, KIT and AXL

Locally Advanced; Neoadjuvant

I

AEs

NCT03299946

2018

 Nivolumab plus Bevacizumab

PD-1 + VEGFA

Advanced or Metastatic

I

AEs/MTD or RP2D

NCT03382886

2018

 Durvalumab plus Cabozantinib

PD-L1 + VEGFR, MET, RET, KIT and AXL

Advanced;

Second-line

I

MTD

NCT03539822

2018

 Nivolumab plus Vorolanib

PD-1 + VEGFR, PDGFR

/

I

RP2D

NCT03511222

2018

 PDR001 plus Sorafenib

PD-1 + VEGFRs, KIT, PDGFRs, and RAF

Advanced;

First-line

I

AEs

NCT02988440

2017

 Pembrolizumab plus Regorafenib

PD-1 + VEGFR1–3, PDGFR-β, FGFR1, KIT, RET and B-RAF

Advanced;

First-line

I

AEs/DLTs

NCT03347292

2018

 Durvalumab plus Ramucirumab

PD-L1 + VEGFR2

Advanced or metastatic

I

DLTs

NCT02572687

2016

 IBI310 plus Sintilimab

CTLA-4 + PD-1

Advanced;

First-line

III

OS/ORR

NCT04720716

2021

 Nivolumab plus Ipilimumab

PD-1 + CTLA-4

Advanced;

First-line

III

OS

NCT04039607

2019

 Durvalumab plus Tremelimumab

PD-L1 + CTLA-4

Advanced;

First-line

III

OS

NCT03298451

2017

 TSR-042 plus TSR-022

PD-1 + TIM-3

Locally advanced or metastatic

II

ORR

NCT03680508

2018

 Pembrolizumab plus Bavituximab

PD-1 + PS

Advanced;

First-line

II

ORR

NCT03519997

2018

 Nivolumab plus BMS-986205

PD-1 + IDO1

Advanced;

First-line

I/II

AEs/ORR

NCT03695250

2018

 Pembrolizumab plus Epacadostat

PD-1 + IDO1

/

I/II

DLTs/ORR

NCT02178722

2014

 Pembrolizumab plus INCAGN01876 plus Epacadostat

PD-1 + GITR+IDO1

Advanced

I/II

AEs/ORR

NCT03277352

2017

 Nivolumab plus Galunisertib

PD-1 + TβRI

Advanced; Recurrent

I/II

MTD

NCT02423343

2015

 Nivolumab plus Avadomide

PD-1 + CRBN

Unresectable

I/II

DLT/AEs/ORR

NCT02859324

2016

 Pembrolizumab plus VSV-IFNβ-NIS

PD-1 + Oncolytic virus

Refractory

I

ORR/AEs

NCT03647163

2019

 Durvalumab plus Guadecitabine

PD-L1 + DNMT

Advanced; Metastatic

I

AEs/ORR

NCT03257761

2018

 Pembrolizumab plus XL888

PD-1 + Hsp90

Advanced; Metastatic

I

RP2D

NCT03095781

2017

 Pembrolizumab plus Vaccine

PD-1 + Modified Vaccinia Virus Ankara Vaccine Expressing p53

Unresectable;

Second-line

I

Tolerability

NCT02432963

2015

 PDR001 plus NIS793

PD-1 + TGF-β

Advanced

I

DLTs/AEs

NCT02947165

2017

 Nivolumab plus SF1126

PD-1 + PI3K

Advanced

I

DLT

NCT03059147

2017

 Apatinib plus Capecitabine

VEGFR-2 + DNA/RNA Synthesis

Advanced

II

TTP

NCT03114085

2017

 Temsirolimus plus Sorafenib

mTOR+VEGFRs, KIT, PDGFRs, and RAF

Advanced;

First-line

II

TTP

NCT01687673

2012

 Trametinib plus Sorafenib

MEK 1/2 + VEGFRs, KIT, PDGFRs, and RAF

Advanced

I

MTD

NCT02292173

2014

 CVM-1118 plus Sorafenib

VM + VEGFRs, KIT, PDGFRs, and RAF

Advanced

II

ORR

NCT03582618

2018

 mFOLFOX plus Sorafenib

DNA Synthesis+VEGFRs, KIT, PDGFRs, and RAF

/

II

TTP

NCT01775501

2013

Erlotinib plus Bevacizumab

EGFR+VEGFA

Advanced;

Second-line

II

PFS (16 W)

NCT01180959

2011

 TRC 105 plus Sorafenib

Endoglin+VEGFRs, KIT, PDGFRs, and RAF

/

I/II

MTD/ORR

NCT02560779

2016

 Enzalutamide plus Sorafenib

AR + VEGFRs, KIT, PDGFRs, and RAF

Advanced;

First-line

I/II

PFS

NCT02642913

2015

 Napabucasin or Amcasertib plus Sorafenib

STAT3, cancer stemness kinase+VEGFRs, KIT, PDGFRs, and RAF

Advanced;

First-line

I/II

RP2D/AEs/AA

NCT02279719

2014

 ADI-PEG 20 plus FOLFOX

Arginine+DNA Synthesis

Advanced

I/II

ORR

NCT02102022

2014

 FATE-NK100 plus Cetuximab or Trastuzumab

NK cell immunotherapy+EGFR or EGFR2

EGFR1+ or HER2+; Advanced

I

DLT

NCT03319459

2018

 Navitoclax plus Sorafenib

Bcl-2 + VEGFRs, KIT, PDGFRs, and RAF

Relapsed or refractory

I

MTD/AEs

NCT02143401

2014