Table 3.

Clinical trials involving TLRs 7/8 agonists and antagonists.

Ligands (synonyms or explanations given once)	In combination with	TLRs	Investigators	Pathologies Applications	Typea	Phase	Clinical Trial Identification	Statusb
Agonists
852A PF-04878691 S-32865 3M852A		7	3M Pharmaceuticals	Inoperable melanoma (Unresectable metastatic cutaneous melanoma)	D	II	EudraCT2004-003910-41	C
852A		7	Masonic Cancer Center University of Minnesota, Pfizer	Breast, ovarian, endometrial, and cervical cancer	D	II	NCT00319748	C
852A		7	Pfizer	Hepatitis C Virus (Multiple-dose escalation study, safety, tolerability, pharmacokinetics and pharmacodynamics evaluation in healthy volunteers)	D	I	NCT00810758	C
852A		7	Pfizer	Inoperable metastatic Melanoma	D	II	NCT00189332	C
Imiquimod R837	radiotherapy	7	University of Oklahoma, NCI	Melanoma and metastatic cancer	D	I	NCT00453050	O
Imiquimod	cyclophosphamide and radiotherapy	7	NYU Langone Health, New York University School of Medicine, NCI	Metastatic and recurrent breast cancer	A	I and II	NCT01421017	C
Imiquimod		7	New York University School of Medicine, NYU Langone Health	Breast cancer Breast neoplasms	D	II	NCT00899574	C
Imiquimod		7	The University of Hong Kong	Influenza viral infection	A	III	NCT02103023	C
Imiquimod		7	Medical University of Vienna	Human Papillomavirus	D	II	NCT00941811	C
Imiquimod		7	Graceway Pharmaceuticals, LLC	Actinic keratosis	D	III	NCT00894647	C
Imiquimod		7	MEDA Pharma GmbH & Co. KG	Actinic keratosis	D	IV	NCT00777127	C
Imiquimod		7	Mochida Pharm. Co Ltd, 3 M Pharm., Valeant Pharm. International Inc, iNova Pharm. Pty Ltd, Intendis GmbH, Meda AB	Keratosis, mycosis fungoides, verruca vulgaris, condyloma, basal cell carcinoma, and molluscum contagiosum infection	A	Approved NCT01453179
Imiquimod		7	3M Pharmaceuticals	Papilloma viruses		Approved
Imiquimod		7	University of Michigan	Photoaged skin and normal skin	A	Unknown	NCT02889159	O
Imiquimod		7	3M Pharmaceuticals	Anogenital Human Papillomavirus Infection, Anal Condyloma	D	III	NCT03289260	O
Imiquimod	intradermal HBVv	7	The University of Hong Kong	Renal failure	A	II and III	NCT02621112	C
Imiquimod		7	The University of Hong Kong	Intra-dermal with Topical Imiquimod Pretreatment vs. intra-muscular Hepatitis B Vaccination in Inflammatory bowel disease Patients	A	II and III	NCT04083157	O
Imiquimod	influenza vaccine	7	The University of Hong Kong	Influenza Viral Infections	A	III	NCT02103023	C
Imiquimod	influenza vaccine	7	The University of Hong Kong	Chronic illness	A	Unknown	NCT01508884	C
Imiquimod	5-FU	7	3M Pharm. National Cancer Institute	high-grade cervical intraepithelial neoplasia	A	I	NCT03196180	O
Imiquimod	PD-1 blockade	7	University of Virginia, Theraclion	Advanced Solid Tumors (Melanoma, Breast, Merkel Cell, Squamous Cell, Non-Small Cell Lung, Cervical, Urothelial, Ovarian, Hepatocellular, Small-cell Lung, Gastric and Esophageal Cancers)	A	I	NCT04116320	O
Imiquimod	doxepin	7	Aalborg University	Itch (to verify if imiquimod mechanism of action follows the histaminergic or non-histaminergic pathway by using the anti-histamine drug doxepin)	A	Unknown	NCT03943407	O
Imiquimod	Abraxane	7	University of Washington	Breast Cancer	D	II	NCT00821964	C
Imiquimod		7	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Cervical Cancer	D	I	NCT00788164	O
Imiquimod		7	Massachusetts General Hospital	Neurofibromatosis	D	I	NCT00865644	C
Imiquimod		7	St. Justine’s Hospital	Hemangioma	D	II	NCT00601016	C
Imiquimod	tazarotene	7	University of Utah	Lentigo Maligna	D	Not applicable	NCT00707174	C
Imiquimod	Peptide-based vaccine	7	University of Virginia	Melanoma	D	I	NCT01264731	C
Imiquimod	Peptide-based vaccine	7	Ludwig Institute for Cancer Research	Melanoma	A	I	NCT00142454	C
Imiquimod	Peptide-based vaccine	7	National Cancer Institute	Melanoma	A	I	NCT00118313	C
Imiquimod	Melan-A VLP vaccine, Montanide	7	Cytos Biotechnology AG	Melanoma	A	II	NCT00651703	C
Imiquimod	Dendritic cell/tumor fusion vaccine, GM-CSF	7	Beth Israel Deaconess Medical Center	Ovarian Cancer Primary Peritoneal Cancer Fallopian Tube Cancer	D	II	NCT00799110	O
Imiquimod		7	Memorial Sloan Kettering Cancer Center	Vulvar Cancer	D	Non Applicable	NCT00504023	C
Imiquimod		7	Medical University of Vienna	Cervical Intraepithelial Neoplasia	D	II, III	NCT00941252	C
Imiquimod		7	Medical University of Graz	Lentigo Maligna	D	II, III	NCT01088737	O
Imiquimod		7	Jerry Marsden, University Hospital Birmingham NHS Foundation Trust	Lentigo Maligna	D	IV	NCT01161888	C
Imiquimod		7	Medical University of Graz	Vulvar intraepithelial Neoplasia	D	III	NCT01861535	O
Imiquimod		7	University Medical Center Nijmegen	Paget Disease	D	III	NCT02385188	C
Imiquimod	Radiotherapy	7	Melanoma and Skin Cancer Trials Limited	Lentigo Maligna	D	III	NCT02394132	O
TMX-101 (liquid formulation of imiquimod) Vesimune		7	Telormedix SA	non-invasive bladder cancer, including patients with CIS bladder cancer.	A	II	NCT01731652	C
TMX-101		7	Telormedix SA	Non-Muscle-Invasive Bladder Cancer	D	I	EudraCT2009-014757-33	C
Resiquimod R848		7/8	3M Pharmaceuticals	Hepatitis C Infection Herpes	D	II/III	–	S
Resiquimod		7/8	University of British Columbia	Influenza vaccination in seniors	A	I	NCT01737580	C
Resiquimod		7/8	Vincent S. Fan, VA Puget Sound Health Care System, University of Washington, Novartis Pharmaceuticals	Chronic Obstructive Pulmonary Disease, Chronic Bronchitis	A	Unknown (observational non-interventional trial)	NCT02637219	C
Resiquimod	NY-ESO-1 protein	7/8	CRI New York City, Icahn School of Medicine at Mount Sinai	Tumors expressing NY-ESO-1 protein	A	I	NCT00821652	C
Resiquimod		7/8	M.D. Anderson Cancer Center, Houston, Texas	Melanoma	A	II	NCT00960752	O
Resiquimod	poly-ICLC	7/8	Jonsson Comprehensive Cancer Center	Glioma, anaplastic astrocytoma, anaplastic astro-oligodendroglioma	A	II	NCT01204684	O
Resiquimod		7/8	University of Virginia	Melanoma and its metastatic mucosal variants	A	I and II	NCT02126579	C
AZD8848 DSP-3025 AZD-3025		7	Sumitomo Dainippon Pharma Co., Ltd.	Healthy volonteers	D	I	NCT01124396	C
AZD8848		7	AstraZeneca	Allergy Asthma	D	II	NCT00999466	C
GSK2245035		7	GSK, PATH	Asthma Rhinitis	D	II	NCT01607372	C
GSK2245035		7	GSK	Mild asthma and allergic rhinitis (to examine the safety and effects on the immune system)	D	II	NCT01788813	C
GSK2245035		7	GSK	Allergy rhinitis, asthma, and respiratory tract allergy	D	I and II	NCT02833974	C
GSK2245035		7	GSK	Allergy rhinitis	D	II	EudraCT2015-005645-31	C
GSK2445035		7	GSK	Allergic Rhinitis (to collect tolerability, pharmacokinetic and pharmacodynamic information)	D	I	NCT01480271	C
GS-9620 vesatolimod		7	Gilead Sciences	Chronic hepatitis B in virally suppressed patients	A	II	NCT02166047 GS-US-283-1059	C
GS-9620	Tenofovir Disoproxil Fumarate	7	Gilead Sciences	Chronic hepatitis B	D	II	NCT02579382	C
GS-9620		7	AELIX Therapeutics	HIV vaccine	A	II	EudraCT2018-002125-30	S
Single or multiple GS-9620		7	Gilead Sciences	Hepatitis B	A	I	NCT01590654	C
GS-9620	ARV Regimen	7	Gilead Sciences	Latent reservoir HIV (suppressive ART)	D	I	NCT02858401	C
GS-9620	ART	7	Gilead Sciences	Latent reservoir HIV (HIV infected controllers)	D	I	NCT03060447	O
RO7020531		7	Hoffmann-La Roche	Healthy volunteers	D	I	NCT03530917	C
RO7020531		7	Hoffmann-La Roche	Chronic Hepatitis B	D	I	NCT02956850	O
RO6864018 (aka-ANA773, ANA773, RG7795)		7	Hoffmann-La Roche	Healthy volunteers	D	I	NCT02015715	C
ANA773		7	Anadys Pharmaceuticals	Cancer	A	I	EudraCT2011-000728-14	O
ANA773		7	Anadys Pharmaceuticals	Hepatitis C	A	I	EudraCT2011-000728-14	O
ANA773		7	Hoffmann-La Roche	Chronic Hepatitis B	D	II	NCT02391805	C
RO6871765 or RO7011785		7	Hoffmann-La Roche	Chronic Hepatitis B	D	Unknown	NCT02498275	T
DSP-0509	Pembrolizumab	7	Boston Biomedical, Inc Syneos Health	Advanced Solid Tumors	D	I and II	NCT03416335	O
NJH395		7	Novartis Pharmaceuticals	non-breast HER2+ Malignancies (NJH395 = Immune stimulator antibody conjugate (ISAC), consisting of a monoclonal antibody which targets HER2 conjugated to an immune-stimulatory agent)	A	I	NCT03696771	O
BNT411	with or without atezolizumab, carboplatin and etoposidz	7	BioNTech Small Molecules GmbH	Solid Tumor Extensive-stage Small Cell Lung Cancer (combination with combination with cytotoxic therapies and immune checkpoint inhibitors)	D	I and II	NCT04101357	O
TQ-A3334 JNJ-4964 AL-034	entecavir	7	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	Chronic Hepatitis B	D	II	NCT04180150	O
LHC165	PDR-1	7	Novartis Pharmaceuticals	Advanced Solid Tumors	D	I	NCT03301896	O
Hydroxychloroquine		7/9	Seoul National University Hospital	Dry Eye/dry mouth of Primary Sjogren’s Syndrome, Autoimmune Diseases	D	III	NCT01601028	C
MEDI9197	durvalumab and/or palliative radiation	7/8	MedImmune LLC	Solid tumor CTLC	D	I	NCT02556463	T (compagny strategy)
NKTR-262	bempegaldesleukin with or without nivolumab	7/8	Nektar Therapeutics	Locally Advanced or Metastatic Solid Tumor Malignancies (Melanoma, Merkel Cell, Triple Negative Breast, Head and Neck Squamous Cell, Renal Cell and Colorectal Cancers)	D	I and II	NCT03435640	O
CV8102	IMA970A Cyclophosphamide	7/8	CureVac	Early and intermediate stages hepatocellular carcinoma	A	I and II	NCT03203005	O
CV8102	anti-PD-1	7/8	CureVac	Solid tumors (Melanoma, Squamous Cell Carcinoma of the Skin, Squamous Cell of Head and Neck Carcinoma, Adenoid Cystic)	D	I	NCT03291002	O
VTX-1463		8	VeniRx Pharmaceuticals Inc	Allergy	D	I		O
VTX-2337 Motolimod	cetuximab	8	University of Washington, NCI	Different stages of locally advanced, recurrent, or metastatic squamous cell cancer of the head and neck	A	I	NCT01334177	C
VTX-2337	Cetuximab, Nivolumab	8	Celgene	Squamous Cell Carcinoma of the head and neck	D	I	NCT02124850	T
VTX-2337	cyclophosphamide	8	Mayo Clinic, NCI	Metastatic, persistent, recurrent or progressive solid tumors (various types and stages of colorectal, pancreatic, breast, melanoma, non-small cell lung carcinoma, pancreatic, renal cell carcinoma and solid neoplasm)	A	I	NCT02650635	T
VTX-2337	paclitaxel or doxorubicin	8	Gynecologic Oncology Group, NCI	Recurrent or persistent ovarian epithelial, fallopian tube, or peritoneal cavity cancer	A	I	NCT01294293	C
VTX-2337	radiotherapy	8	VentiRx Pharmaceuticals Inc, Stanford University, Celgene	Low grade B-Cell lymphoma	A	I and II	NCT01289210	T (The study was stopped due to slow rate of recruitment)
VTX-2337	cisplatin	8	VentiRx Pharmaceuticals Inc	Carcinoma, squamous cell of head and neck	A	II	NCT01836029	C
VTX-2337	doxorubicin	8	Gynecologic Oncology Group, Celgene	Recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer	A	II	NCT01666444	C
VTX-2337	anti-PD- L1 antibody durvalumab (MEDI4736)	8	Ludwig Institute for Cancer Research, MedImmune LLC, VentiRx Pharmaceuticals Inc, CRI New York City	Ovarian cancer	A	I and II	NCT02431559	O
VTX-2337	anti-PD- L1 antibody nivolumab	8	Celgene	Squamous cell carcinoma of the head and neck	A	I	NCT03906526	O
GS-9688	TAF	8	Gilead Sciences	Chronic Hepatitis B	D	II	NCT03615066	O
Antagonists
IMO-8400 Bazlitoran		7/8/9	Idera Pharmaceuticals, Inc	Dermatomyositis		II	NCT02612857	O
IMO-8400		7/8/9	Idera Pharmaceuticals, Inc	Diffuse large B-cell lymphoma	D	I/II	NCT02252146	C
IMO-8400		7/8/9	Idera Pharmaceuticals, Inc	Waldenstrom’s macroglobulinemia	A	I/II	NCT02092909	T (lack of efficacy)
IMO-8400		7/8/9	Idera Pharmaceuticals, Inc	Plaque psoriasis	D	II	NCT01899729	C
IMO-3100		7/8	Idera Pharmaceuticals, Inc	SLE Rheumatoid Arthritis Multiple sclerosis		Preclinical	–	–
IRS-954 DV-1079		7/9	Dynavax Technologies	SLE		Preclinical	–	–
IRS-954		7/9	Dynavax Technologies	HIV		Preclinical	–	–
CPG-52364		7/8/9	Pfizer	SLE	D	I	NCT00547014	O

^aD for drug, A for adjuvant.

^bC for completed, T for terminated, O for ongoing, S for suspended.