Table 1.
Target | Drug | Immune checkpoint inhibitor | Clincal trial | Cancer type | Phase | |
DPP8, DPP9, and FAP inhibitor | Talabostat | Pembrolizumab | NCT04171219 | Solid neoplasm | Phase II | |
Biogenesis | Pembrolizumab | NCT03910660 | Prostate cancer/neuroendocrine tumors/small cell carcinoma | Phase I/II | ||
IL6 | Tocilizumab | Nivolumab, ipilimumab | NCT04258150 | Pancreatic cancer | Phase II | |
Nivolumab, ipilimumab | NCT03999749 | Melanoma | Phase II | |||
STAT3 | BBI-608 (napabucasin) | Pembrolizumab | NCT02851004 | Colorectal cancer | Phase I/II | |
Ipilimumab/nivolumab/pembrolizumab | NCT02467361 | Cancers | Phase I/II | |||
Nivolumab | NCT04299880 | Oncology | Phase I | |||
Nivolumab | NCT03047839 | Colorectal cancer | Phase II | |||
IL1-beta | Canakinumb | Spartalizumab | NCT04028245 | Renal cell carcinoma | Early phase I | |
Spartalizumab | NCT03742349 | Triple-negative breast cancer | Phase I | |||
Pembrolizumab | NCT03968419 | Non-small cell lung cancer | Phase II | |||
Pembrolizumab | NCT03631199 | Non-small cell lung cancer | Phase III | |||
RIP-1 | GSK3145095 | Pembrolizumab | NCT03681951 | Advenced solid tumors | Phase II | |
Recruitment | LXR-alpha/beta | RGX-104 | Nivolumab, ipilimumab, pembrolizumab | NCT02922764 | Malignant neoplasms | Phase I |
CXCR4/CXCL12 | BL-8040/BKT140 | Pembrolizumab | NCT02907099 | Metatstatic pancreatic adenocarcinoma | Phase II | |
Pembrolizumab | NCT02826486 | Metatstatic pancreatic denocarcinoma | Phase II | |||
AMD3100/plerixafor | Pembrolizumab | NCT04058145 | Metastatic head and neck squamous cell carcinoma | Phase II | ||
X4P-001 | Pembrolizumab | NCT02823405 | Advenced melanoma | Phase I | ||
Nivolumab | NCT02923531 | Clear cell renal cell carcinoma | Phase Ib/II | |||
CXCR4/CXCR7 | NOX-A12/olaptesed | Pembrolizumab | NCT03168139 | Metastatic colorectal cancer/metastatic pancreatic cancer | Phase Ib/II | |
CXCR1/2 | SX-682 | Pembrolizumab | NCT03161431 | Advenced melanoma | Phase I | |
Navarixin | Pembrolizumab | NCT03473925 | Non-small cell lung cancer/castration-resistant prostate cancer/MSS colorectal cancer | Phase II | ||
IL8 | BMS-986253 | Nivolumab | NCT04123379 | Non-small cell lung cancer and HNCC | Phase II | |
CCR2/5 | BMS-813160 | Nivolumab | NCT03184870 | Metastatic colorectal cancer and pancreatic cancer | Phase I/II | |
NCT04123379 | Non-small cell lung cancer and HNCC | Phase II | ||||
CCR5 | vicriviroc | Pembrolizumab | NCT03631407 | Advenced MSS colorectal cancer | Phase II | |
C5aR | IPH5401 | Durvalumab | NCT03665129 | Non-small cell lung cancer/hepatocellular carcinoma | Phase I | |
PI3K inhibitors | PI3K alpha | Duvelisib | Pembrolizumab | NCT04193293 | Head and neck small cell cancer | Phase I/II |
PI3K-beta | GSK2636771 | Pembrolizumab | NCT03131908 | Melanoma | Phase I/II | |
PI3K alpha, beta, gamma, delta | Copanlisib/BAY80−6946/aliqopa | Nivolumab | NCT03502733 | Solid tumor and lymphoma | Phase I | |
Nivolumab | NCT03711058 | MSS proficient solid tumors | Phase I/II | |||
Nivolumab | NCT03735628 | Non-small cell lung cancer/head and neck small cell cancer/colorectal cancer/hepatocellular carcinoma | Phase I/II | |||
Durvalumab | NCT03842228 | Solid tumors | Phase I | |||
Nivolumab±ipilimumab | NCT04317105 | Solid tumors | Phase I/II | |||
PI3K delta/gamma and low affinity alpha/beta | Idelalisib / GS-1101/zydelig | Pembrolizumab | NCT03257722 | Non-small cell lung cancer | Phase I/II | |
PI3K-delta | Itacitinib / INCB050465/IBI376 | Pembrolizumab | NCT02646748 | Advanced solid tumors | Phase I | |
Immunosuppressive functions and inhibitory signaling | ARG1 | INCB001158 | Pembrolizumab | NCT02903914 | Metastatic solidd tumors | Phase I/II |
Pembrolizumab | NCT03361228 | Solid tumors | Phase I/II | |||
Pegzilarginase | Pembrolizumab | NCT03371979 | Small cell lung cancer | Phase I/II | ||
COX2 | Celecoxib | Nivolumab | NCT03864575 | ‘Cold’ solid tumors | Phase I/II | |
Nivolumab+Ipilimumab | NCT03728179 | Solid tumors | Phase I/II | |||
PGE2-receptor | Grapiprant/ARY-007 | Pembrolizumab | NCT03696212 | Non-small cell lung cancer | Phase I | |
NCT03658772 | MSS colorectal cancer | Phase I | ||||
NOS | L-NMMA | Pembrolizumab | NCT03236935 | Non-small cell lung cancer/head and neck small cell cancer/classical Hodgkin's lymphoma/urothelial carcinoma/bladder DNA repair-deficiency disorders | Phase I | |
NOS | L-NMMA | Pembrolizumab | NCT04095689 | Triple-negative breast cancer | Phase II | |
CD47 | ALX148 | Pembrolizumab | NCT03013218 | Metastatic cancer/solid tumor/advanced cancer/non-Hodgkin's lymphoma | Phase I | |
SIRPa | TTI-621 | Pembrolizumab | NCT02890368 | Melanoma, Merkel-cell carcinoma/squamous cell carcinoma/breast carcinoma/HPV-related malignant neoplasm/soft tissue sarcoma | Phase I | |
Nivolumab | NCT02663518 | Haematologic/solid tumor | Phase I | |||
TJ011133/TJC4 | Pembrolizumab | NCT03934814 | Solid tumors/lymphoma | Phase I | ||
ILT4 | MK-4830 | Pembrolizumab | NCT04165083 | Advenced solid tumors | Phase I |
FAP, fibroblast activation protein; HNCC, head and neck cancer; MSS, microsatellite intability; PI3K, phosphatidylinositol-3-kinase.