Table 3 Therapeutics targeting immuno-epigenetics and cytokines

azacytidine

Pfizer

small molecule inh

FDA Approved

II

Pancreatic Cancer

anti-PD-1 (Pembrolizumab)

NCT03264404

Active, not recruiting

CC-486

Pfizer

small molecule inh

FDA Approved

II

NSCLC

anti-PD-1 (Pembrolizumab)

NCT02546986

Active, not recruiting

decitabine

Janssen-Cilag/Otsuka Pharmaceutical

small molecule inh

FDA Approved

II

Breast Cancer

anti-PD-1 (Pembrolizumab), chemotherapy

NCT02957968

Active, not recruiting

guadecitabine

Astex Pharmaceuticals

small molecule inh

Phase III

I

Lung Cancer

anti-PD-1 (Pembrolizumab), HDAC inh (Mocetinostat)

NCT03220477

Active, not recruiting

ASTX727

Astex Pharmaceuticals

small molecule inh

FDA Approved

I/II

Melanoma

anti-PD-1 (Nivolumab)

NCT05089370

Recruiting

class I HDACs

Romidepsin (FK228, Depsipeptide, FR 901228, NSC 630176)

Celgene Corporation

small molecule inhibitor

FDA approved

III

T-Cell Lymphoma

aurora A kinase inhibitor (Alisertib), chemotherapy

NCT01482962

Completed

Entinostat (SNDX-275, MS 275, MS 27-275, KHK2375)

Syndax Pharmaceuticals

small molecule inhibitor

III

III

Breast Cancer

hormone therapy (Exemestane)

NCT03538171

Active, not recruiting

Mocetinostat (MGCD0103, MG-0103)

Mirati Therapeutics

small molecule inhibitor

II

II

UC

–

NCT02236195

Completed

Domatinostat (4SC-202)

4SC AG

small molecule inhibitor

II

II

Gastrointestinal Cancer

anti-PD-L1 (Avelumab)

EMERGE

NCT03812796

Recruiting

Nanatinostat (Tractinostat, VRx-3996, CHR-3996)

Viracta Therapeutics

small molecule inhibitor

II

II

EBV-associated Lymphoma

anti-virus (Valganciclovir)

NAVAL-1

NCT05011058

Recruiting

OKI-179

OnKure

small molecule inhibitor

I/II

I/II

Melanoma

MEK1/2 inhibitor (Binimetinib)

NCT05340621

Recruiting

Zabinostat (CXD101)

Celleron Therapeutics

small molecule inhibitor

I/II

I/II

CRC

anti-PD-1 (Nivolumab)

CAROSELL

NCT03993626

Active, not recruiting

Class II HDAC6

Ricolinostat (ACY-1215)

Regenacy Pharmaceuticals

small molecule inhibitor

I/II

I/II

MM

–

ACY-1215

NCT01323751

Completed

Citarinostat (ACY-241)

Celgene Corporation

small molecule inhibitor

I

I

MM

IMiD (Pomalidomide), chemotherapy

NCT02400242

Active, not recruiting

KA-2507

Karus Therapeutics Limited

small molecule inhibitor

II

I

Solid Tumors

–

NCT03008018

Completed

Class I and II HDACs

Vorinostat (Suberoylanilide hydroxamic acid, Zolinza, L-001079038)

Merck & Co.

small molecule inhibitor

FDA approved

III

CTCL

anti-CCR4 (KW-0761)

MAVORIC

NCT01728805

Completed

Tucidinostat (Chidamide, HBI-8000)

HUYA Bioscience International

small molecule inhibitor

III

III

DLBCL

anti-CD20 (Rituximab), chemotherapy

DEB

NCT04231448

Recruiting

Class I, II and IV HDACs (pan-HDAC)

Panobinostat (LBH 589, Farydak, MTX110)

Novartis/Secura Bio

small molecule inhibitor

FDA approved

III

MM

proteasome inhibitor (Bortezomib), Dexamethasone

PANORAMA-1

NCT01023308

Completed

Abexinostat (PCI 24781, CRA-24781)

Xynomic Pharmaceuticals

small molecule inhibitor

III

III

RCC

TKI (Pazopanib)

RENAVIV

NCT03592472

Recruiting

Pracinostat (SB-939)

MEI Pharma

small molecule inhibitor

III

II

MDS

chemotherapy

MEI-005

NCT01993641

Completed

Resminostat (4SC-201, RAS2410)

4SC AG

small molecule inhibitor

II

II

HCC

Raf inhibitor (Sorafenib)

Shelter

NCT00943449

Completed

HDAC and other molecules

Fimepinostat (CUDC-907)

Curis

PI3K/HDAC small molecule dual inhibitor

II

II

DLBCL

–

NCT02674750

Completed

BET proteins (pan-BET)

INCB057643

Incyte Corporation

small molecule inhibitor

I/II

I

Myeloid Neoplasms

stem cell transplantation, JAK1/2 Inhibitor (Ruxolitinib)

NCT04279847

Recruiting

RO6870810 (RG 6146)

Roche

small molecule inhibitor

I

I

MM

anti-CD38 (Daratumumab)

NCT03068351

Completed

Molibresib (I-BET-762, GSK525762)

GlaxoSmithKline

small molecule inhibitor

II

II

Hematological malignancies

–

NCT01943851

Completed

Mivebresib (ABBV-075)

AbbVie

small molecule inhibitor

I

I

Myelofibrosis

chemotherapy, JAK1/2 inhibitor (Ruxolitinib)

NCT04480086

Active, not recruiting

Trotabresib (CC-90010)

Celgene Corporation

small molecule inhibitor

I

I

Solid tumors

–

NCT03220347

Recruiting

Pelabresib (CPI-0610)

MorphoSys

small molecule inhibitor

III

III

Myelofibrosis

JAK1/2 inhibitor (Ruxolitinib)

MANIFEST-2

NCT04603495

Recruiting

BMS-986158

Bristol Myers Squibb

small molecule inhibitor

I/II

I/II

MM

EZH2 inhibitor (Tazemetostat), MEK1/2 inhibitor (Trametinib), dexamethasone

NCT05372354

Not yet recruiting

ODM-207

OrionPharma

small molecule inhibitor

I/II

I/II

Solid Tumors

–

BETIDES

NCT03035591

Completed

BRD4

PLX2853

Daiichi Sankyo group

small molecule inhibitor

I/II

I/II

Ovarian Cancer

chemotherapy

NCT04493619

Active, not recruiting

PLX51107

Daiichi Sankyo group

small molecule inhibitor

I

I

AML, MDS

chemotherapy

NCT04022785

Recruiting

BI 894999

Boehringer Ingelheim

small molecule inhibitor

I

I

Solid tumors

–

NCT02516553

Completed

AZD5153 (SRA 515)

AstraZeneca

small molecule inhibitor

I/II

I/II

AML

BCL2 inhibitor (Venetoclax)

NCT03013998

Recruiting

EZH2

Tazemetostat

Epizyme Inc

small molecule inhibitor

FDA approved

III

FL

IMiD (Lenalidomide), anti-CD20 (Rituximab)

NCT04224493

Recruiting

CPI-0209

Constellation Pharmaceuticals Inc

small molecule inhibitor

I/II

I/II

Solid Tumors and lymphoma

–

NCT04104776

Recruiting

LSD1

Ladademstat (ORY1001, RG-6016)

Oryzon Genomics

TCP-based irreversible LSD1 inhibitor

II

II

SCLC, Neuroendocrine Cancer

chemotherapy

NCT05420636

Not yet recruiting

INCB059872

Incyte Corporation

TCP-based irreversible LSD1 inhibitor

I/II

I/II

Solid Tumors, Hematological Neoplasms

chemotherapy, anti-PD-1 (Nivolumab)

NCT02712905

Active, not recruiting

Pulrodemstat (CC-90011)

Celgene Corporation

reversible LSD1 inhibitor

II

II

Malignancies

anti-PD-1 (Nivolumab)

NCT04350463

Recruiting

Seclidemstat (SP-2577)

Salarius Pharmaceuticals

reversible LSD1 inhibitor

I/II

I/II

CML, MDS

chemotherapy

NCT04734990

Recruiting

PRMT5

Pemrametostat (GSK-3326595)

GlaxoSmithKline, Epizyme

small molecule inhibitor

II

II

Breast Cancer

–

OTT-19-06

NCT04676516

Not yet recruiting

PF-06939999

Pfizer

small molecule inhibitor

I

I

Solid Tumors

chemotherapy

NCT03854227

Active, not recruiting

PRT543

Prelude Therapeutics

small molecule inhibitor

I

I

Malignancies

–

NCT03886831

Active, not recruiting

IL-2

aldesleukin

Clinigen/Novartis

rhIL-2

FDA approved

III

Melanoma

chemotherapy, G-CSF (Filgrastim), IFN-α

PROCLIVITY01

NCT00006237

Completed

THOR-707 (SAR444245)

Synthorx Inc

non-α IL-2 variant

II

II

HNSCC

anti-PD-1 (Pembrolizumab), anti-EGFR (Cetuximab)

NCT05061420

Recruiting

SHR-1916

Jiangsu Hengrui Medicine

non-α IL-2 variant

I

I

Solid Tumors

–

NCT04842630

Recruiting

Nemvaleukin alfa (ALKS 4230)

Alkermes plc

non-α IL-2 variant-IL-2Rα fusion protein (blocking the IL-2Rα binding)

III

III

Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer

anti-PD-1 (Pembrolizumab)

ARTISTRY-7

NCT05092360

Recruiting

Simlukafusp alfa (SIM, FAP-IL2v, RO6874281)

Roche

IL-2 variant-anti-FAP antibody fusion protein

II

II

Head and Neck, esophageal and cervical Cancers

anti-PD-L1 (Atezolizumab)

NCT03386721

Completed

Eciskafusp Alfa (PD-1–IL2v)

Hoffmann-La Roche

IL-2 variant-anti-PD-1 antibody fusion protein

I

I

Solid Tumors

anti-PD-1 (Atezolizumab)

NCT04303858

Recruiting

CUE-101 (E7-pHLA-IL2-Fc)

Cue Biopharma

IL-2 variant-HLA complex+ HPV16 E7 peptide epitope fusion protein

I

I

HPV16 + HNSCC

anti-PD-1 (Pembrolizumab)

NCT03978689

Recruiting

GI-101 (CD80-IgG4-IL-2-Fc)

GI Innovation

IL-2 variant-anti-CD80 antibody fusion protein

I/II

I/II

Solid Tumors

anti-PD-1 (Pembrolizumab), multi-kinase inh (Lenvatinib), radiation

NCT04977453

Recruiting

Cergutuzumab amunaleukin (CEA–IL2v)

Hoffmann-La Roche

IL-2 variant-anti-CEA antibody fusion protein

I

I

Solid tumors

anti-PD-1 (Atezolizumab)

NCT02350673

Completed

MDNA11

Medicenna Therapeutics

IL-2 variant-rhalbumin fusion protein

I/II

I/II

Solid Tumors

checkpoint inhibitor

ABILITY

NCT05086692

Recruiting

Darleukin (L19-IL2, Daromun, Philogen)

Philogen SpA

IL-2-anti-ED-B fibronectin antibody fusion protein

III

III

Melanoma

ADC (L19-TNF)

Pivotal

NCT02938299

Recruiting

STK-012

Synthekine

α/β-IL-2 variant

I

I

Solid Tumors

anti-PD-1 (Pembrolizumab)

NCT05098132

Recruiting

RG6292 (RO7296682)

Hoffmann la Roche

anti-CD25 mAb

I

I

Solid Tumors

anti-PD-L1 (Atezolizumab)

NCT04642365

Recruiting

XTX202

Xilio Therapeutics

conditionally-activated IL-2

I/II

I/II

Solid Tumors

–

NCT05052268

Recruiting

IL-15

NIZ985 (hetIL-15)

Admune Therapeutics

IL-15-IL-15Rα fusion protein

I

I

Solid Tumors

anti-PD-1 (Spartalizumab)

NCT02452268

Completed

XmAb24306 (RO7310729, RG6323)

Xencor Inc

IL-15-IL-15Rα fusion protein

I

I

Solid Tumors

anti-PD-L1 (Atezolizumab)

NCT04250155

Recruiting

Inbakicept (N-803, ALT-803)

ImmunityBio

IL-15-IL-15Rα fusion protein

III

III

NSCLC

anti-PD-1 (Pembrolizumab), chemotherapy

QUILT 2.023

NCT03520686

Recruiting

SHR-1501

Jiangsu Hengrui Medicine

IL-15-IL-15Rα fusion protein

I

I

Malignancies

anti-PD-L1 (SHR-1316)

NCT03995472

Recruiting

BJ-001

BJ Bioscience

IL-15-IL-15Rα-integrin-binding motif fusion protein

I

I/II

Solid Tumors

anti-EGFR (Cetuximab)

NCT04616196

Recruiting

NKTR-255

Nkarta Therapeutics

polymer conjugated IL-15

II

II

UC

anti-PD-L1 (Avelumab)

JAVELIN Bladder Medley

NCT05327530

Not yet recruiting

IL-10

Ilodecakin (Pegilodecakin, AM0010)

ARMO BioSciences

PEGylated human IL-10

III

III

Pancreatic Cancer

chemotherapy

Sequoia

NCT02923921

Completed

IL-12

NHS-IL12 (M9241)

National Cancer Institute (USA)

IL-12-anti-DNA-histone H1 complex mAb fusion protein

II

II

Bowel Cancers, CRC

cancer vaccine (CV301), PD-L1 x TGFβ bsAb (MSB0011359C), IL-15 superagonist (N-803)

NCT04491955

Recruiting

SON 1010 (IL12FHAB)

Sonnet Biotherapeutics

IL-12-FHAB fusion protein

I

I

Solid Tumors

–

NCT05352750

Recruiting

GEN-1 (EGEN-001)

Celsion Corporation

plasmid-encoded IL-12

II

II

Ovarian Carcinoma, Fallopian Tube Carcinoma, Primary Peritoneal Carcinoma

–

NCT01118052

Completed

MEDI 0457 (INO-9012)

AstraZeneca/Inovio Pharmaceuticals

plasmid-encoded IL-12

II

II

HPV-associated Cancers

anti-PD-L1 (Durvalumab)

NCT03439085

Active, not recruiting

Tavokinogene telseplasmid

OncoSec Medical

plasmid-encoded IL-12

II

II

Melanoma

anti-PD-1 (Pembrolizumab)

Keynote695

NCT03132675

Recruiting

INXN 2001 (ad-RTS-hIL-12)

ZIOPHARM Oncology Inc

adenovirus encoding activable IL-12

II

II

Glioblastoma

anti-PD-1 (Cemiplimab)

NCT04006119

Completed

TGF-β

NIS793

Novartis

antagonistic pan-TGF-β mAb

III

III

PDAC

chemotherapy

daNIS-2

NCT04935359

Recruiting

AVID-200 (BMS-986416)

Formation Biologics, Bristol-Myers Squibb

TGF-βR ECD-Fc fusion protein (TGF-β1/3 Trap)

I

I

Solid Tumors

anti-PD-1 (Nivolumab)

NCT04943900

Recruiting

Trabedersen

Oncotelic Therapeutics

antisense against TGF-β2

II

II

Glioblastoma

–

NCT00431561

Completed

TGF-βR

Vactosertib (TEW-7197)

MedPacto

small molecule inhibitor

II

II

CRC

anti-PD-1 (Pembrolizumab)

NCT03844750

Recruiting

YL-13027

Shanghai Yingli Pharmaceutical

small molecule inhibitor

I

I

Solid Tumors

–

NCT03869632

Recruiting

Activation of L-TGF-β

SRK-181

Scholar Rock

selective L-TGF-β1 antagonistic mAb

I

I

Solid Tumors

anti-PD-1/PD-L1

DRAGON

NCT04291079

Recruiting

ABBV-151

AbbVie

selective L-TGF-β1 antagonistic mAb

I

I

Solid Tumors

anti-PD-1 (Budigalimab)

NCT03821935

Recruiting

PF-06940434

Pfizer

αvβ8 integrin mAb

I

I

Solid Tumors

anti-PD-1 (Sasanlimab)

NCT04152018

Recruiting

CXCR4

Balixafortide (POL6326)

Spexis

small molecule inhibitor

III

III

Breast Cancer

microtubule inhibitor (Eribulin)

FORTRESS

NCT03786094

Active, not recruiting

Motixafortide (BL-8040)

Biokine Therapeutics, BioLineRx

small molecule inhibitor

III

III

MM

G-GSF, stem cell transplantation

GENESIS

NCT03246529

Active, not recruiting

Mavorixafor (X4P-001)

Sanofi, X4 Pharmaceuticals

small molecule inhibitor

I/II

I/II

ccRCC

VEGFR1/2/3 inhibitor (Axitinib)

NCT02667886

Active, not recruiting

CXCR2

AZD5069

AstraZeneca

small molecule inhibitor

I/II

I/II

Solid Tumors

anti-PD-L1 (MEDI4736), anti-CTLA-4 (Tremelimumab)

SCORES

NCT02499328

Active, not recruiting

SX-682

Syntrix Biosystems Inc

CXCR1/2 small molecule inhibitor

I/II

I/II

CRC

anti-PD-1 (Nivolumab)

STOPTRAFFIC-1

NCT04599140

Recruiting