Table 1.
Clinical trial combining epigenetic targetings with immunotherapies
| Type of epigenetic drugs | Epigenetic drug (targets) | Immunotherapy | Cancer type | Trial ID |
|---|---|---|---|---|
| DNMT inhibitors | Azacytidine | Nivolumab (anti-PD1) | AML, NSCLC, Osteosarcoma | NCT02397720 [136]; NCT03825367 [137]; NCT01928576 [138]; NCT03628209 [139] |
| Pembrolizumab (anti-PD1) | AML,CRC/microsatellite-stable CRC,HNSCC, Melanoma,MDS,NSCLC, PDAC,Ovarian primary peritoneal or fallopian tube cancer |
NCT02546986 [140]; NCT02959437 [141]; NCT02845297 [142]; NCT03769532 [143]; NCT02260440 [144]; NCT02512172 [145]; NCT03094637 [146]; NCT02816021 [147]; NCT03264404 [148]; NCT02900560 [149] |
||
| Visilizumab(anti-PD1) | Relapsed Adult AML | NCT04722952 [150] | ||
| Atezolizumab (anti-PDL1) | MDS | NCT02508870 [151] | ||
| Avelumab (anti-PDL1) | AML | NCT02953561 [152]; NCT03390296 [153] | ||
| Durvalumab (anti-PDL1) | MDS, AML, NSCLC, Head and neck cancer, Breast cancer | NCT02775903 [154]; NCT02117219 [155]; NCT02250326 [156]; NCT03019003 [157]; NCT02811497 [158] | ||
| Ipilimumab (anti-CTLA4) | MDS | NCT02530463 [159] | ||
| Tremelimumab (anti-CTLA4) | MDS, Head and neck cancer | NCT02117219 [155]; NCT03019003 [157] | ||
| Pembrolizumab and epacadostat (IDO-1 inhibitor) | Advanced Solid Tumors, Non-Small Cell Lung Cancer, Microsatellite-Stable CRC | NCT02959437 [141] | ||
| Decitabine (DNMT1) | Camrelizumab (anti-PD1) | Hodgkin Lymphoma, PMBCL | NCT04514081 [160]; NCT03250962 [161]; NCT03346642 [162] | |
| Nivolumab(anti-PD1) | Non-small Cell Lung Cancer | NCT02664181 [163] | ||
| Pembrolizumab (anti-PD1) | AML, MDS, CNS solid tumors, NSCLC, Breast cancer | NCT02996474 [164]; NCT03969446 [165]; NCT02957968 [166]; NCT03445858 [167]; NCT03233724 [168]; | ||
| Avelumab (anti-PDL1) | AML | NCT03395873 [169] | ||
| pilimumab (anti-CTLA4) | MDS, AML | NCT02890329 [170] | ||
| Decitabine(with Chidamide, a HDAC inhibitor) | Camrelizumab (anti-PD1) | Hodgkin Lymphoma | NCT04514081 [160] | |
| Guadecitabine(SGI-110) | Nivolumab (anti-PD1) | CRC | NCT03576963 [171] | |
| Pembrolizumab (anti-PD1) | NSCLC, CRPC | NCT02998567 [172]; NCT02901899 [173] | ||
| Atezolizumab (Anti-PD-L1) | AML, MDS, urothelial carcinoma,Ovarian Carcinoma, Fallopian Tube Carcinoma, Primary Peritoneal Carcinoma | NCT02892318 [174]; NCT02935361 [175]; NCT03179943 [176]; NCT03206047 [177] | ||
| Durvalumab (anti-PDL1) | Renal cancer, hepatocellular carcinoma, PDAC | NCT03308396 [178]; NCT03257761 [179] | ||
| Ipilimumab (anti-CTLA4) | Metastatic Melanoma | NCT02608437 [180] | ||
| Guadecitabine( with Mocetinostat HDAC inhibitor) | Pembrolizumab (anti-PD1) | NSCLC | NCT03220477 [181] | |
| EZH2 inhibitors | Tazemetostat | Pembrolizumab (anti-PD1) | Urothelial carcinoma | NCT03854474 [182] |
| Atezolizumab (anti-PDL1) | DLBCL | NCT02220842 [183] | ||
| CPI-1205 | Ipilimumab (anti-CTLA4) | Advanced solid tumours | NCT03525795 [184] | |
| BET inhibitor | INCB057643 | Pembrolizumab and epacadostat (IDO-1 inhibitor) | Advanced Solid Tumors, Non-Small Cell Lung Cancer, Microsatellite-Stable CRC | NCT02959437 [141] |
| BMS-986158 | Nivolumab (anti-PD1) | haematologic malignancies | NCT02419417 [185] | |
| LSD inhibitor | INCB059872 | Pembrolizumab and epacadostat (IDO-1 inhibitor) | Advanced Solid Tumors, Non-Small Cell Lung Cancer, Microsatellite-Stable CRC | NCT02959437 [141] |
| Nivolumab (anti-PD1) | SCLC | NCT02712905 [186] | ||
| HDAC inhibitor | Chidamide with Decitabine | Immune checkpoint inhibitors(anti-PD1/PD-L1/CTLA4 antibodies) | Non-Hodgkin Lymphoma and advanced solid tumors | NCT05320640 [187] |
| Entinostat | Nivolumab (anti-PD1) | PDAC | NCT03250273 [188] | |
| Pembrolizumab (anti-PD1) | Advanced solid tumours, Lymphomas, melanoma, bladder cancer, MDS | NCT03179930 [189]; NCT02936752 [190]; NCT03978624 [191]; NCT02437136 [192]; NCT02909452 [193]; NCT03765229 [194] | ||
| Nivolumab and ipilimumab | Renal cell carcinoma | NCT02453620 [195]; NCT03552380 [196] | ||
| Avelumab (anti-PDL1) | Ovarian cancer | NCT02915523 [197] | ||
| Mocetinostat | Nivolumab (anti-PD1) | NSCLC | NCT02954991 [198] | |
| Pembrolizumab (anti-PD1) | NSCLC | NCT03220477 [181] | ||
| Durvalumab (anti-PDL1) | NSCLC | NCT02805660 [199] | ||
| Nivolumab and ipilimumab | Melanoma | NCT03565406 [200] | ||
| Vorinostat | Pembrolizumab (anti-PD1) | HNSCC, NSCLC, renal or urothelial cell carcinoma, Breast cancer, Glioblastoma, DLBCL, Hodgkin Lymphoma | NCT02638090 [201]; NCT03426891 [202]; NCT03150329 [203]; NCT02538510 [204]; NCT02619253 [205]; NCT02395627 [206] |
AML: acute myeloid leukaemia; BET: Bromodomain and extra-terminal; CNS: central nervous system; CRC: colorectal cancer; CRPC: castration-resistant prostate cancer; CTLA4: cytotoxic T lymphocyte-associated protein 4; DLBCL: diffuse large B cell lymphoma; DNMT: DNA methyltransferase; EZH2: enhancer of zeste homologue 2; HDAC: histone deacetylase; HNSCC: head and neck squamous cell carcinoma; MDS: myelodysplastic syndrome; NSCLC: non-small-cell lung cancer; PDAC: pancreatic ductal adenocarcinoma; PMBCL: primary mediastinal large B cell lymphoma; SCLC: small-cell lung cancer