Table 2 Clinical trials combining epigenetic targeting agents and immune checkpoint inhibitors

From: Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets

Epigenetic targeting agents

Immune checkpoint inhibitors

Conditions and trial ID

DNMTi

 Azacytidine

Pembrolizumab (anti-PD1)

CRC (NCT02260440, NCT02512172), NSCLC, microsatellite-stable CRC, HNSCC, urothelial carcinoma and melanoma (NCT02959437), AML (NCT02845297, NCT04284787, NCT03769532), NSCLC (NCT02546986), myelodysplastic syndrome (MDS) (NCT03094637), melanoma (NCT02816021), PDAC (NCT03264404), platinum-resistant ovarian cancer (NCT02900560), relapsed/refractory Hodgkin lymphoma (NCT05355051)

 

Nivolumab (anti-PD1)

AML (NCT02397720, NCT03825367, NCT04913922), NSCLC (NCT01928576), MDS (NCT02530463) osteosarcoma (NCT03628209), hodgkin lymphoma (NCT05162976), HNSCC (NCT05317000)

 

Durvalumab (anti-PD-L1)

MDS (NCT02281084, NCT02117219, NCT02775903), AML (NCT02775903), peripheral T-cell lymphoma (NCT03161223), NSCLC (NCT02250326), pancreatic cancer (NCT04257448), microsatellite-stable CRC, ovarian cancer and estrogen receptor-positive and HER2-negative breast cancer (NCT02811497)

 

Camrelizumab (anti-PD1)

AML (NCT05772273), peripheral T-Cell lymphoma (NCT05559008)

 

Atezolizumab (anti-PD-L1)

MDS (NCT02508870)

 

Avelumab (anti-PD-L1)

AML (NCT03390296)

 

Spartalizumab (anti-PD1)

MDS/AML (NCT03066648)

 

Tremelimumab (anti-CTLA4)

MDS (NCT02117219)

 

Ipilimumab (anti-CTLA4)

MDS (NCT02530463), AML(NCT02397720)

 

PF-04518600 (anti-OX40)

AML (NCT03390296)

 Decitabine

Pembrolizumab

AML (NCT02996474, NCT03969446), MDS (NCT03969446), peripheral T-cell lymphoma/cutaneous T-cell lymphoma (NCT03240211), CNS solid tumors and lymphomas (NCT03445858), NSCLC (NCT03233724), locally advanced HER2-negative breast cancer (NCT02957968), metastatic triple-negative breast cancer (NCT05673200)

 

Nivolumab

Mucosal melanoma (NCT05089370), AML (NCT04277442), NSCLC (NCT02664181), MDS/AML (NCT02664181)

 

Durvalumab

head and neck cancer (NCT03019003),

 

Camrelizumab

Hodgkin lymphoma (NCT04510610, NCT03250962, NCT04514081, NCT04233294), primary mediastinal large B-cell lymphoma (NCT03346642), AML(NCT04353479)

 

Spartalizumab

MDS (NCT05201066), MDS/AML (NCT03066648)

 

Ipilimumab

Relapsed or refractory myelodysplastic syndrome or AML (NCT02890329)

 Guadecitabine

Pembrolizumab

Lung cancer (NCT03220477), NSCLC/castration-resistant prostatic cancer (NCT02998567), ovarian, primary peritoneal or fallopian tube cancer (NCT02901899)

 

Nivolumab

Melanoma, NSCLC (NCT04250246)

 

Durvalumab

Advanced kidney cancer (NCT03308396), extensive-stage small cell lung cancer (NCT03085849), hepatocellular carcinoma, gallbladder cancer, pancreatic cancer, intrahepatic cholangiocarcinoma (NCT03257761)

 

Atezolizumab

Chronic myelomonocytic leukemia, MDS and AML (NCT02935361), AML (NCT02892318), ovarian, fallopian tube, or primary peritoneal cancer (NCT03206047), urothelial carcinoma (NCT03179943)

 

Tremelimumab

Extensive-stage small cell lung cancer (NCT03085849)

 

Ipilimumab

Melanoma (NCT02608437), melanoma/NSCLC (NCT04250246)

HDACi

 Vorinostat

Pembrolizumab

HNSCC or salivary gland cancer (NCT02538510), NSCLC (NCT02638090), renal or urothelial cell carcinoma (NCT02619253), glioblastoma (NCT03426891), diffuse large B-cell lymphoma, follicular lymphoma or Hodgkin lymphoma (NCT03150329), squamous cell carcinoma (NCT04357873), breast cancer (NCT04190056)

 Entinostat

Pembrolizumab

MDS (NCT02936752), advanced solid tumors (NCT02909452), lymphoma (NCT03179930), NSCLC, melanoma and CRC (NCT02437136), melanoma (NCT03765229), uveal melanoma (NCT02697630), bladder cancer (NCT03978624)

 

Nivolumab

CNS tumor, solid tumor (NCT03838042), renal cell carcinoma (NCT03552380), HER2-negative breast cancer (NCT02453620), non-small cell lung cancer (NCT01928576), cholangiocarcinoma or PDAC (NCT03250273)

 

Ipilimumab

HER2-negative breast cancer (NCT02453620), renal cell carcinoma (NCT03552380)

 

Atezolizumab

Triple-negative breast cancer (NCT02708680), lung cancer (NCT04631029), hormone receptor-positive, HER2-negative breast cancer (NCT03280563), renal cell carcinoma (NCT03024437)

 

Avelumab

Ovarian, peritoneal and fallopian tube cancer (NCT02915523)

 Panobinostat

Ipilimumab

Melanoma (NCT02032810)

 

Nivolumab

Triple-negative breast cancer (NCT02393794)

 

Durvalumab

Lymphoma (NCT03161223)

 Mocetinostat

Pembrolizumab

Lung cancer (NCT03220477)

 

Nivolumab

NSCLC (NCT02954991)

 ACY-241

Nivolumab

NSCLC (NCT02635061), Melanoma (NCT02935790)

 

Ipilimumab

Melanoma (NCT02935790)

 Valproic acid

Avelumab

Virus-associated cancers (NCT03357757)

 inostamustine

Nivolumab

Advanced melanoma (NCT03903458)

 Chidamide

Nivolumab

Melanoma, renal cell carcinoma, NSCLC (NCT02718066), advanced melanoma (NCT04674683)

 

Pembrolizumab

NSCLC (NCT05141357)

 Abexinostat

Pembrolizumab

Solid tumors (NCT03590054)

 Domatinostat

Avelumab

Merkel cell carcinoma (NCT04393753), Gastrointestinal cancers (NCT03812796)

 

Nivolumab and ipilimumab

Melanoma (NCT04133948)

 Nanatinostat

Pembrolizumab

EBV-positive solid tumors (NCT05166577)

BET inhibitor

 BMS-986158

Nivolumab

Selected advanced tumors (NCT02419417)

EZH2 inhibitor

 Tazemetostat

Pembrolizumab

Urothelial carcinoma (NCT03854474), HNSCC (NCT04624113)

 

Atezolizumab

Follicular lymphoma and diffuse large B-cell lymphoma (NCT02220842)

 

Nivolumab and ipilimumab

Malignant rhabdoid tumor, atypical teratoid rhabdoid tumor, epithelioid sarcoma, and chordoma (NCT05407441)

 

Durvalumab

Advanced solid tumors (NCT04705818)

 CPI-1205

Ipilimumab

Advanced solid tumors (NCT03525795)

KDM1A inhibitor

 IMG-7289

Atezolizumab

Extensive-stage small cell lung cancer (NCT05191797)