Table 1.
Ongoing clinical trials targeting metabolic circuits in combination with immune checkpoint inhibitors.
| Metabolic Targets | Immune Checkpoint Inhibitors | Cancer Types | Phase | Status | Clinical Trial Identifier |
|---|---|---|---|---|---|
| Arginine pathway inhibitors | |||||
|
L-NMMA
(NO synthase inhibitor) |
Pembrolizumab | TNBC | II | Not yet recruiting | NCT04095689 |
|
CB-1158
(Arginase inhibitor) |
Pembrolizumab | Solid tumors | I/II | Active, not recruiting | NCT02903914 |
| IDO inhibitors | |||||
|
Epacadostat
(INCB024360; IDO-1 inhibitor) |
Pembrolizumab | HNSCC | III | Active, not recruiting | NCT03358472 |
| Pembrolizumab | RCC | III | Active, not recruiting | NCT03260894 | |
| Pembrolizumab | GIST | II | Active, not recruiting | NCT03291054 | |
| Pembrolizumab | MIBC | II | Not yet recruiting | NCT03832673 | |
| Pembrolizumab | Thymic cancer | II | Active, not recruiting | NCT02364076 | |
| Pembrolizumab | Metastatic pancreatic cancer | II | Recruiting | NCT03006302 | |
| Pembrolizumab | Sarcoma | II | Active, not recruiting | NCT03414229 | |
| Ipilimumab + Nivolumab |
Solid tumors | I/II | Active, not recruiting | NCT03347123 | |
|
Linrodostat
(BMS-986205; IDO-1 inhibitor) |
Nivolumab | Melanoma | III | Active, not recruiting | NCT03329846 |
| Nivolumab | Endometrial cancer | II | Recruiting | NCT04106414 | |
| Nivolumab | HNSCC | II | Recruiting | NCT03854032 | |
| Nivolumab | HCC | I/II | Recruiting | NCT03695250 | |
| Nivolumab | NSCLC | I/II | Recruiting | NCT02658890 | |
| Nivolumab | Solid tumors | I/II | Active, not recruiting | NCT03792750 | |
| PD-L1/IDO peptide vaccine | Nivolumab | Melanoma | I/II | Recruiting | NCT03047928 |
|
KHK2455
(IDO-1 inhibitor) |
Avelumab | Bladder cancer | I | Recruiting | NCT03915405 |
| Inhibitors of COX enzymes | |||||
|
Aspirin
(COX-1 and COX-2 inhibitor) |
Atezolizumab | Ovarian cancer | II | Active, not recruiting | NCT02659384 |
| Avelumab | TNBC | II | Not yet recruiting | NCT04188119 | |
| Ipilimumab + Pembrolizumab | Melanoma | II | Active, not recruiting | NCT03396952 | |
| Pembrolizumab | CRC | II | Recruiting | NCT03638297 | |
| Pembrolizumab | Cervical/Uterine cancer | II | Recruiting | NCT03192059 | |
|
Celecoxib
(COX-2 inhibitor) |
Pembrolizumab | Brain metastasis from TNBC or HER2+ breast cancer | II | Not yet recruiting | NCT04348747 |
| Nivolumab | Solid tumors | II | Not yet recruiting | NCT03864575 | |
|
Grapiprant
(EP4 antagonist) |
Pembrolizumab | NSCLC | I/II | Recruiting | NCT03696212 |
| Pembrolizumab | Microsatellite stable CRC | I | Recruiting | NCT03658772 | |
| Glutamine and glutamate pathway inhibitors | |||||
|
Telaglenastat
(CB-839; glutaminase inhibitor) |
Pembrolizumab | NSCLC | II | Recruiting | NCT04265534 |
| Nivolumab | Melanoma or NSCLC | I/II | Active, not recruiting | NCT02771626 | |
|
DRP-104
(glutamine antagonist) |
Atezolizumab | Solid tumors | I/II | Recruiting | NCT04471415 |
|
IPN60090
(glutaminase inhibitor) |
Pembrolizumab | Solid tumors | I | Recruiting | NCT03894540 |
| Adenosine pathway inhibitors | |||||
|
Oleclumab
(MEDI9447; anti-CD73 antibody) |
Durvalumab |
Luminal B breast cancer | II | Active, not recruiting | NCT03875573 |
| Durvalumab | TNBC | I/II | Recruiting | NCT03616886 | |
|
AB928
(A2AR and A2BR antagonist) |
Atezolizumab | CRC | I/II | Recruiting | NCT03555149 |
|
Ciforadenant
(CPI-444; A2AR antagonist) |
Atezolizumab | RCC | I | Recruiting | NCT02655822 |
|
AZD4635
(A2AR antagonist) |
Durvalumab | NSCLC or CRC | I | Active, not recruiting | NCT02740985 |
|
IPH5201
(Anti-CD39 antibody) |
Durvalumab | Solid tumors | I | Recruiting | NCT04261075 |
|
LY3475070
(CD73 inhibitor) |
Pembrolizumab | Advanced cancers | I | Recruiting | NCT04148937 |
|
CPI-006
(Anti-CD73 antibody) |
Pembrolizumab | Advanced cancers | I | Recruiting | NCT03454451 |
|
EOS100850
(A2AR antagonist) |
Pembrolizumab | Solid tumors | I | Recruiting | NCT03873883 |
| Inhibitors of glucose metabolism | |||||
|
Metformin
(Multiple effects of glucose metabolism) |
Pembrolizumab | HNSCC | II | Recruiting | NCT04414540 |
| Nivolumab | NSCLC | II | Active, not recruiting | NCT03048500 | |
| Durvalumab | HNSCC | I | Recruiting | NCT03618654 | |
| Pembrolizumab | Melanoma | I | Recruiting | NCT03311308 | |
| Inhibitors of lipid metabolism | |||||
|
TPST-1120
(PPAR α antagonist) |
Nivolumab | Advanced cancers | I | Recruiting | NCT03829436 |
TNBC, triple-negative breast cancer; HNSCC, head and neck squamous cell carcinoma; RCC, renal cell carcinoma; GIST, gastrointestinal stromal tumor; NSCLC, non-small cell lung cancer; MIBC, muscle-invasive bladder cancer; HCC, hepatocellular carcinoma; CRC, colorectal cancer.