Epigenetic mechanisms of liver tumor resistance to immunotherapy

Table 1 Main clinical trials on immunotherapies and epigenetic agents in monotherapies or in combination

Clinical trial	Phase	Drugs	Line/setting	Cancer type
NCT033834581	3	Nivolumab vs placebo	ADJ	HCC
NCT038670841	3	Pembrolizumab vs placebo	ADJ	HCC
NCT030623581	3	Pembrolizumab + BSC vs placebo + BSC	ADJ	HCC
NCT034127731	3	Tislelizumab vs sorafenib	1	HCC
NCT037557912	3	Cabozantinib + atezolizumab vs sorafenib	1	HCC
NCT044870672	3	Atezolizumab + bevacizumab	1	HCC
NCT043107092	2	Regorafenib + nivolumab	1	HCC
NCT044433092	1-2	Lenvatinib + camrelizumab	1	HCC
NCT043932202	2	Nivolumab + bevacizumab	1	HCC
NCT037789573	3	TACE + durvalumab + bevacizumab	1	HCC
NCT042461773	3	Lenvatinib + pembrolizumab + TACE	1	HCC
NCT043401933	3	Nivolumab + ipilimumab + TACE	1	HCC
NCT042688883	2-3	Nivolumab + TACE/TAE	1	HCC
NCT034821023	2	Durvalumab + tremelimumab + radiation	1	HCC
NCT032984514	3	Durvalumab + tremelimumab and durvalumab vs sorafenib	1	HCC
NCT040396074	3	Nivolumab + ipilimumab vs SOC	1	HCC
NCT036057065	3	Camrelizumab + FOLFOX4	1	HCC
NCT034398915	2	Sorafenib + nivolumab	1	HCC
NCT032577616	1	Guadecitabine + durvalumab	2	Liver, pancreatic, bile duct or gallbladder cancer
NCT028160216	2	Azacitidine + pembrolizumab	1	Melanoma
NCT045412776	2	Tislelizumab + DNMTi +/- chemotherapy	1	AML
NCT025304636	2	Nivolumab and/or ipilimumab +/- azacitidine	1/2	Myelodysplastic Syndrome
NCT035523806	2	Entinostat + nivolumab + ipilimumab	2	Kidney
NCT031799306	2	Entinostat + pembrolizumab	2	Lymphoma
NCT026976306	2	Pembrolizumab + entinostat	1	Metastatic uveal melanoma
NCT032502736	2	Entinostat + nivolumab	2	Cholangiocarcinoma and pancreatic adenocarcinoma
NCT029155236	1/2	Avelumab +/- entinostat	1/2	Ovarian cancer
NCT038380426	1/2	Nivolumab + entinostat	1/2	CNS, solid tumors
NCT030244376	1/2	Atezolizumab with entinostat and bevacizumab	1/2	Kidney
NCT019285766	2	Nivolumab +/- entinostat + azacitidine	2	NSCLC
NCT029018996	2	Guadecitabine and pembrolizumab	2	Ovarian, primary peritoneal, or fallopian tube cancer
NCT031799436	2	Atezolizumab + guadecitabine	2	Urothelial carcinoma
NCT035769636	1/2	Guadecitabine + nivolumab	2	Metastatic colorectal cancer
NCT033083966	1/2	Durvalumab + guadecitabine	1/2	Kidney
NCT029353616	1/2	Guadecitabine + atezolizumab	2	Myelodysplastic syndrome or chronic myelomonocytic leukemia

¹Immune checkpoint inhibitor (ICI) monotherapy.

²Combination ICI with anti-angiogenic agents.

³Combination ICI with locoregional treatment.

⁴ICI combination.

⁵Other ICI combinations.

⁶ICI + epigenetic drugs.

AML: Acute myeloid leukemia; BSC: Best supportive care; CNS: Central nervous system; HCC: Hepatocellular carcinoma; NSCLC: Non-small-cell lung carcinoma; SOC: Standard of care; TACE: Transarterial chemoembolization; TAE: Transarterial embolization.