. 2019 Oct 16;3:15–23. doi: 10.1016/j.iotech.2019.10.001

Table 1.

Clinical trials of intratumoural immunotherapy of compounds that activate nucleic acid sensing pattern recognition receptors (PRRs) alone or in combination with checkpoint inhibitors.

PRR activator	Combination agent	Patient population	Clinical stage	Clinical trial number/status
TLR9 agonist^f
IMO-2125	Ipilimumab	Anti-PD-1 refractory melanoma	Phase 3	NCT03445533 ^a
	Ipilimumab or pembrolizumab	Metastatic melanoma	Phase 1/2	NCT02644967 ^b
	Ipilimumab + nivolumab	Solid tumours	Phase 2	NCT03865082 ^c
	Monotherapy	Melanoma, advanced solid tumours	Phase 1b	NCT03052205 ^b
SD-101	Pembrolizumab	Metastatic melanoma, recurrent/metastatic SCCHN	Phase 1b/2	NCT02521870 ^b
	Pembrolizumab + radiation	Hormone-naive OMPC	Phase 2	NCT03007732 ^a
	BMS986178 (anti-OX40 antibody)	Advanced solid malignancies	Phase 1	NCT03831295 ^a
	BMS986178 + radiation	Low-grade B-cell NHL	Phase 1	NCT03410901 ^a
	Epacadostat + radiation	Advanced solid tumours and lymphoma	Phase 1/2	NCT03322384 ^a
	Ipilimumab + radiation	MALT lymphoma, NMZL, MZL, SLL, grade 1/2 FL and SMZL	Phase 1/2	NCT02254772 ^d
	Pembrolizumab	Breast cancer	Phase 2	NCT01042379 ^a
CMP-001	Pembrolizumab	Melanoma	Phase 1	NCT02680184 ^a
	Pembrolizumab	Advanced melanoma	Phase 1b	NCT03084640 ^a
	Nivolumab	Melanoma with lymph node disease	Phase 2	NCT03618641 ^a
	Radiosurgery + nivolumab + ipilimumab	Metastatic CRC	Phase 1	NCT03507699 ^a
	Atezolizumab	NSCLC	Phase 1	NCT03438318 ^a
AST-008^f	Pembrolizumab	Advanced/metastatic melanoma, MCC, SCCHN, cSCC and solid tumours	Phase 1b/2	NCT03684785 ^a
MGN1703^f	Ipilimumab	Melanoma, advanced solid tumours	Phase 1	NCT02668770 ^a
TLR3 agonist
Poly-ICLC (Hiltonol)	Monotherapy	Prostate cancer	Phase 1	NCT03262103 ^a
	Tremelimumab/durvalumab (MEDI4736)	SCCHN, MCC, CTCL, breast cancer, melanoma, renal cancer, bladder cancer, prostate cancer, testicular cancer and other solid tumours	Phase 1/2	NCT02643303 ^a
	Monotherapy (in situ vaccination)	Melanoma, head and neck cancer, sarcoma and non-melanoma skin cancers	Phase 2	NCT02423863 ^a
	Pembrolizumab	MRP colon cancer	Phase 1/2	NCT02834052 ^a
BO-112^g	Pembrolizumab, nivolumab	Aggressive solid tumours	Phase 1	NCT02828098 ^b
TLR7/8 agonists
NKTR-262^g (TLR7/8)	Peg-CD-122 agonist (NKTR-214) + nivolumab	Melanoma, MCC, TNBC, RCC, CRC, ovarian cancer, urothelial carcinoma and sarcoma	Phase 1/2	NCT03435640 ^a
CV8102^g^,^h (TLR7/8/RIG-I)	Anti-PD-1 antibody	Advanced melanoma, SCC, SCCHN or ACC	Phase 1	NCT03291002 ^a
LHC-165 (TLR7)	Spartalizumab	Solid tumours	Phase 1/1b	NCT03301896 ^a
MEDI9197 (TLR7/8)	Durvalumab	CTCL and solid tumours	Phase 1	NCT02556463 ^e
RIG-I agonist
RGT100 (MK-4621)	Monotherapy	Advanced solid tumours	Phase 1/2	NCT03065023 ^e
	Pembrolizumab	Advanced solid tumours	Phase 1/1b	NCT03739138 ^a
STING agonist
ADU-S100/MIW815	Spartalizumab	Advanced/metastatic solid tumours or lymphomas	Phase 1	NCT03172936 ^a
	Pembrolizmab	Metastatic/recurrent SCCHN	Phase 2	NCT03937141 ^a
	Monotherapy and with ipilimumab	Advanced/metastatic solid tumours and lymphomas	Phase 1	NCT02675439 ^a
MK-2118	Monotherapy and with pembrolizumab	Advanced/metastatic solid tumours	Phase 1	NCT03249792 ^a
MK-1454	Monotherapy and with pembrolizumab	Advanced/metastatic solid tumours or lymphomas	Phase 1	NCT03010176 ^a
SB 11285ⁱ	Nivolumab	Melanoma, SCCHN and solid tumours	Phase 1	NCT04096638 ^c
GSK3745417ⁱ	Monotherapy and with pembrolizumab	Solid tumours	Phase 1	NCT03843359 ^a

ACC, adenoid cystic carcinoma; CRC, colorectal cancer; CTCL, cutaneous T-cell lymphoma; FL, follicular lymphoma; MALT lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; MCC, Merkel cell carcinoma; MRP, mismatch repair proficient; MZL, marginal zone lymphoma; NHL, non-Hodgkin lymphoma; NMZL, nodal marginal zone B-cell lymphoma; NSCLC, non-small cell lung cancer; OMPC, oligometastatic prostate cancer; RCC, renal cell carcinoma; SCCHN, squamous cell carcinoma of head and neck; SLL, small lymphocytic lymphoma; SMZL, splenic marginal zone lymphoma; TNBC, triple negative breast cancer.

Recruiting.

Active, not recruiting.

Not yet recruiting.

Completed.

Terminated.

Additional TLR9 agonists in clinical trials include DV281 by inhalation, and IT AST-008 and MGN1703 are in early trials with no data reported yet.

Multiple modes of action.

Single-stranded RNA-based compound.

ⁱ

By intravenous administration.