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. 2025 Oct 8;24:249. doi: 10.1186/s12943-025-02460-1

Table 2.

Overview of clinical trials targeting key immunometabolic checkpoints

Immunometabolic checkpoints Drug Treatment Tumor type Phase Status Clinical trials
IDO1 Epacadostat With pembrolizumab GIST Ⅱ Terminated NCT03291054
IDO1 Epacadostat With pembrolizumab, azacitidine NSCLC, CRC Ⅰ/Ⅱ Terminated NCT02959437
IDO1 Epacadostat With pembrolizumab UC Ⅲ Completed NCT03361865
IDO1 Epacadostat With pembrolizumab mNSCLC Ⅱ Completed NCT03322540
IDO1 Epacadostat With pembrolizumab, Platinum-based Chemotherapy mNSCLC Ⅱ Completed NCT03322566
IDO1 Epacadostat With pembrolizumab mRCC Ⅲ Active, not recruiting NCT03260894
IDO1 Epacadostat With INCB001158, pembrolizumab Advanced solid tumors (mNSCLC, melanoma, UC, SCCHN, SCLC, and CRC) Ⅰ/Ⅱ Terminated NCT03361228
IDO pathway Indoximod With ibrutinib, metronomic cyclophosphamide, etoposide Pediatric brain cancer Ⅰ Recruiting NCT05106296
IDO pathway Indoximod With docetaxel, paclitaxel Metastatic breast cancer Ⅱ Completed NCT01792050
IDO pathway Indoximod With gemcitabine, nab-Paclitaxel Metastatic PC Ⅰ/Ⅱ Completed NCT02077881
IDO pathway Indoximod With temozolomide Malignant brain tumor Ⅰ Completed NCT02502708
IDO pathway Indoximod With pembrolizumab, nivolumab Melanoma Ⅱ Terminated NCT03301636
IDO pathway Indoximod With ipilimumab, nivolumab, pembrolizumab Melanoma Ⅰ/Ⅱ Completed NCT02073123
IDO pathway Indoximod With chemotherapy/radiation Brain tumors, DIPG Ⅱ Recruiting NCT04049669
HIF-1α RO7070179 Monotherapy HCC Ⅰ Completed NCT02564614
HIF-1α EZN-2968 Monotherapy Advanced solid tumors or lymphoma I Completed NCT00466583
HIF-1α PX-478 Monotherapy Advanced solid tumors or lymphoma I Completed NCT00522652
HIF-1α Digoxin Monotherapy BRCA II Completed NCT01763931
HIF-1α CRLX101 With bevacizumab Ovarian/tubal/peritoneal cancer II Completed NCT01652079
Arginase OATD-02 Monotherapy Metastatic solid tumors (CRC, OC, PC or RCC) Ⅰ Recruiting NCT05759923
Arginase CB-1158 Monotherapy or with pembroluzimab Advanced/metastatic solid tumors (mNSCLC, melanoma, UC, CRC, GC, SCCHN and mesothelioma) Ⅰ Completed NCT02903914
Arginase PEG-BCT-100 With capecitabine, oxaliplatin HCC II Completed NCT02089633
Arginase PEG-BCT-100 With doxorubicin HCC I Completed NCT00988195
Arginase PEG-BCT-100 Monotherapy HCC II Completed NCT02089763
Arginase BCT-100-002 Monotherapy HCC I/II Completed NCT01092091
Arginase INCB001158 With FOLFOX, gemcitabine/cisplatin, paclitaxel BTC, CRC, GC, OC, endometrial cancer I/II Completed NCT03314935
Arginase INCB001158 Monotherapy or with retifanlimab Advanced/metastatic solid tumors I Completed NCT03910530
Arginase INCB001158 Monotherapy or with pembrolizumab Advanced/metastatic solid tumors (NSCLC, CRC, SCCHN, RCC, GC, UC and melanoma) I Completed NCT02903914
PPARα TPST-1120 Monotherapy or with nivolumab Advanced tumors (HCC, RCC, NSCLC, GC, CRC, UC, PC, SCCHN) I Completed NCT03829436
PPARα TPST-1120 With atezolizumab, bevacizumab HCC III Not yet recruiting NCT06680258
CD73 Oleclumab With chemotherapy, durvalumab TNBC I/II Active NCT03616886
CD73 Oleclumab With chemotherapy/with or without durvalumab PC I/II Completed NCT03611556
CD73 Oleclumab With durvalumab, gemcitabine, nab-paclitaxel PC II Active NCT04940286
CD73 Oleclumab With durvalumab OC II Completed NCT03267589
CD73 PM1015 Monotherapy Advanced solid tumors I Recruiting NCT05950815
CD73 Sym024 Monotherapy Advanced solid tumors (SCCHN, NSCLC, CRC, GC, CC and esophageal carcinoma) I Completed NCT04672434
CD73 LY3475070 Monotherapy or with pembrolizumab Advanced tumors (PC, BRCA, LC, RCC, OC and melanoma) I Completed NCT04148937
CD73 CPI-006 Monotherapy or with ciforadenant or with pembrolizumab Advanced tumors (NSCLC, RCC, TNBC, CRC, CRC, PC, OC and endometrial cancer) I Completed NCT03454451
CD73 IBI325 Monotherapy or with sintilimab Advanced solid tumors I Completed NCT05119998
CD73 TJ004309 With toripalimab Advanced solid tumors I/II Active NCT04322006
CD38 CID-103 Monotherapy Multiple myeloma I Active NCT04758767
CD38 Multiple universal CAR T cells Monotherapy Acute myeloid leukemia I Recruiting NCT05995041
CD38 STI-6129 Monotherapy Relapsed or refractory multiple myeloma I/II Recruiting NCT05565807
CD38 SAR650984 Monotherapy or with dexamethasone CD38+ hematological malignancies I/II Completed NCT01084252
CD38 Daratumumab With KRAS vaccine and nivolumab NSCLC, PDAC II Recruiting NCT06015724
CD38 Daratumumab Monotherapy Multiple myeloma II Active NCT03236428
CD38 Daratumumab With ibrutinib Chronic lymphocytic leukemia II Active NCT03734198
CD38 Daratumumab With DA- EPOCH Plasmablastic lymphoma I Active NCT04139304
CD38 Daratumumab Monotherapy RCC, mRCC, UC I Completed NCT03473730
PDHK DCA Monotherapy RMBTs I Completed NCT01111097
PDHK DCA Monotherapy Recurrent and metastatic solid tumors I Completed NCT00566410
PDHK DCA Monotherapy SCCHN I Completed NCT01163487
PDHK DCA Monotherapy GBM II Recruiting NCT05120284
PDHK DCA With cisplatin, radiotherapy SCCHN II Completed NCT01386632
GLS CB-839 With sapanisertib NSCLC I Active NCT04250545
GLS CB-839 With palbociclib Advanced solid tumors I/II Completed NCT03965845
GLS CB-839 Monotherapy Tumors with specific mutations II Active NCT03872427
GLS CB-839 With osimertinib NSCLC I/II Active NCT03831932
GLS CB-839 With radiation, temozolomide Astrocytoma I Active NCT03528642
SCD1 MTI-301 Monotherapy Advanced solid tumors I Not yet recruiting NCT06911008
DHODH JBZ-001 Monotherapy Advanced solid tumors and Hematological malignancies I Recruiting NCT06801002
DHODH JNJ-74,856,665 With azacitidine, venetoclax or monotherapy Hematological malignancies I Active NCT04609826
DHODH Leflunomide Monotherapy TNBC I/II Active NCT03709446
AMPK Metformin With FOLFIRI mCRC II Recruiting NCT06826092
AMPK Metformin With standard chemoradiotherapy CRC I/II Recruiting NCT06728982
AMPK Metformin With venetoclax, cytarabine AML II Recruiting NCT06537843
AMPK Metformin With radiotherapy, chemotherapy CC II Recruiting NCT06353061
AMPK Metformin With FOLFOX/XELOX CRC III Completed NCT05921942
AMPK Metformin With tyrosine kinase inhibitors NSCLC III Recruiting NCT05445791
AMPK Metformin With letrozole, abemaciclib Endometrial cancer, OC II Recruiting NCT03675893
AMPK Metformin With chemotherapy PC II Completed NCT01210911

IDO Indoleamine 2;3-dioxygenase, GIST Gastrointestinal stromal tumor, NSCLC Non-small cell lung cancer, LC Lung cancer, CRC Colorectal cancer, UC Urothelial carcinoma, mNSCLC Metastatic non-small cell lung cancer, mRCC Metastatic renal cell carcinoma, SCCHN Squamous cell carcinoma of the head and neck, SCLC Small cell lung cancer, DIPG Diffuse intrinsic pontine glioma, HCC Hepatocellular carcinoma, GC Gastric cancer, OC Ovarian cancer, RCC Renal cell carcinoma, BRCA Breast invasive carcinoma, BTC Biliary tract cancer, PC Pancreatic cancer, TNBC Triple-negative breast cancer, CC Cervical carcinoma, PDAC Pancreatic ductal adenocarcinoma, PDHK Pyruvate dehydrogenase kinase, DCA Dichloroacetate, RMBTs Recurrent malignant brain tumors, GBM Glioblastoma multiforme, AMPK AMP-activated protein kinase, mCRC Metastatic colorectal cancer, AML Acute myeloid leukemia, GLS Glutaminase, SCD1 Stearoyl-CoA desaturase 1, DHODH Dihydroorotate dehydrogenase