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Table 1 Blockades of purinergic signaling registered in clinicaltrials.gov

From: Targeting purinergic pathway to enhance radiotherapy-induced immunogenic cancer cell death

Target Agent Pharmaceutical Supplier Type Dual-specific Delivery method Clinicaltrials.gov Identifier Phase Status Cancer Single agent Combination
A2AR Ciforadenant
(CPI-444)
Corvus Antagonist N/A Orally NCT02655822 I Completed RCC, mCRPC YES Atezolizumab
       NCT04280328 I Completed MM N/A Daratumumab
       NCT03337698 I/II Recruiting NSCLC N/A Atezolizumab
  CS3005 CStone Pharmaceuticals Antagonist N/A Orally NCT04233060 I Completed Advanced solid tumors YES N/A
  Etrumadenant
(AB928)
Arcus Biosciences Antagonist A2AR/
A2BR
Orally NCT03629756 I Completed Advanced malignancies N/A Zimberelimab
       NCT03719326 I Completed TNBC, OC N/A PLD, and/or IPI-549, NP
       NCT03720678 I Completed mGEC, mCRC N/A CT
       NCT03846310 I Active, not recruiting non-squamous NSCLC N/A CT, and/or anti-PD1 antibody
       NCT04892875 I Not yet recruiting Locally advanced head and neck cancers N/A RT, CT, and zimberelimab
       NCT03193190 I/II Active, not recruiting mPDAC N/A Atezolizumab and CT
       NCT03555149 I/II Recruiting mCRC N/A Atezolizumab and regorafenib
       NCT04381832 I/II Recruiting mCRPC N/A Zimberelimab, and/or CT; or with AB680 and/or zimberelimab
       NCT04660812 I/II Recruiting mCRC N/A Zimberelimab and/or CT, bevacizumab, and Regorafenib
       NCT03821246 II Recruiting Localized PC prior to radical prostatectomy N/A Atezolizumab
       NCT04262856 II Recruiting mNSCLC N/A Zimberelimab and domvanalimab
       NCT04791839 II Recruiting previously ICI-treated NSCLC N/A Zimberelimab and domvanalimab
       NCT05024097 II Recruiting Rectal cancer N/A RT, CT, and zimberelimab
       NCT05335941 II Not yet recruiting Previously treated advanced or metastatic MTAP-deficient UC N/A Pemetrexed and zimberelimab
  Imaradenant
(AZD4635)
AstraZeneca Antagonist N/A Orally NCT02740985 I Active, not recruiting Advanced solid malignancies YES Durvalumab, or abiraterone acetate enzalutamide, or docetaxel; with durvalumab and oleclumab
       NCT03980821 I Completed Advanced solid malignancies YES N/A
       NCT04089553 II Active, not recruiting PC N/A Durvalumab or oleclumab
       NCT04495179 II Active, not recruiting mCRPC N/A Durvalumab, ± cabazitaxel
  INCB106385 Incyte Antagonist A2AR/
A2BR
Orally NCT04580485 I Recruiting Advanced solid tumors YES INCMGA00012
  Inupadenant
(EOS100850)
iTeos Therapeutics Antagonist N/A Orally NCT03873883 I Recruiting Adult solid tumors YES Pembrolizumab or CT
       NCT05117177 I Recruiting Adult solid tumors YES N/A
       NCT05060432 I/II Recruiting Advanced solid tumors N/A EOS-448
  PBF-999 Palo Biopharma Antagonist A2AR/
PDE-10
Orally NCT03786484 I Recruiting Advanced solid tumors YES N/A
  Preladenant
(MK-3814)
Merck Antagonist N/A Orally NCT03099161 I Terminateda Advanced solid tumors YES Pembrolizumab
  Taminadenant
(NIR178/PBF-509)
Palo Biopharma
(Novartis)
Antagonist N/A Orally NCT02403193 I Recruiting Advanced solid tumors N/A KAZ954
       NCT03742349 I Recruiting Advanced/relapsed RCC and other malignancies with HIF stablizing mutations N/A PDR001 and DFF332
       NCT04237649 I Recruiting Advanced solid tumors N/A KAZ954
       NCT04895748 I Recruiting Advanced/relapsed RCC and other malignancies with HIF stablizing mutations N/A PDR001 and DFF332
       NCT03207867 II Active, not recruiting Solid tumors and NHL N/A PDR001
A2BR PBF-1129 Palo Biopharma Antagonist N/A Orally NCT03274479 I Recruiting Locally advanced/metastatic NSCLC YES N/A
       NCT05234307 I Not yet recruiting Recurrent/metastatic NSCLC N/A Nivolumab
  TT-4 Tarus Therapeutics Antagonist N/A Orally NCT04976660 I/II Not yet recruiting Advanced selected solid tumors YES N/A
  TT-702 Teon Therapeutics Antagonist N/A Orally NCT05272709 I/II Recruiting Advanced solid tumors YES N/A
CD39 ES002023 Elpiscience Biopharma Antibody N/A I.V NCT05075564 I Recruiting Locally advanced or metastatic solid tumors YES N/A
  IPH5301 Innate Pharma Antibody N/A I.V NCT04261075 I Active, not recruiting Advanced solid tumors YES Durvalumab, ± oleclumab
       NCT05143970 I Recruiting Advanced solid tumors YES CT and trastuzumab
  PUR001 Purinomia Biotech Antibody N/A I.V NCT05234853 I Not yet recruiting Advanced solid tumors YES N/A
  SRF617 Surface Oncology Antibody N/A I.V NCT04336098 I Recruiting Adult solid tumors YES CT or pembrolizumab, or both therapies
       NCT05177770 II Recruiting mCRPC, PC N/A Etrumadenant and zimberelimab
  TTX-030 Trishula Therapeutics
(AbbVie)
Antibody N/A I.V NCT03884556 I Active, not recruiting Advanced cancers YES CT or pembrolizumab
       NCT04306900 I Recruiting Advanced cancers N/A CT, or budigalimab, or pmebrolizumab, or budigalimab and CT
CD73 AK119 Akesobio Antibody N/A I.V NCT04572152 I Recruiting Advanced solid tumors YES AK104
       NCT05173792 I Recruiting Advanced solid tumors YES N/A
  ATG-037 Antengene Antagonist N/A Orally NCT05205109 I Not yet recruiting Locally advanced or metastatic solid tumors YES Pembrolizumab
  BMS-986179 BMS Antibody N/A I.V NCT02754141 I/II Active, not recruiting Malignant solid tumor YES Nivolumab or rHuPH20
  GS-1423 Gilead Sciences Antibody CD73/
TGFβRII
I.V NCT03954704 I Terminatedb Advanced solid tumors YES CT
  HLX23 Henlius Biotech Antibody N/A I.V NCT04797468 I Not yet recruiting Advanced solid tumors YES N/A
  IBI325 Innovent Biologics Antibody N/A I.V NCT05119998 I Recruiting Advanced solid tumors YES Sintilimab
       NCT05246995 I Not yet recruiting Advanced solid tumors N/A Sintilimab
  INCA00186 Incyte Antibody N/A I.V NCT04989387 I Recruiting Advanced solid tumors N/A INCB106385, ± retifanlimab
  JAB-BX102 Jacobio Antibody N/A I.V NCT05174585 I/II Not yet recruiting Advanced solid tumors YES Pembrolizumab
  LY3475070 Eli Lilly Antagonist N/A Orally NCT04148937 I Active, not recruiting Advanced cancers YES Pembrolizumab
  Mupadolimab
(CPI-006)
Corvus Antibody N/A I.V NCT03454451 I Recruiting Advanced cancers YES Ciforadenant or pembrolizumab
  NZV930(SRF373) Surface Oncology Antibody N/A I.V NCT03549000 I Recruiting Advanced malignancies YES PDR001 or NIR178, or both agents
       NCT04237649 I Recruiting Advanced solid tumors N/A KAZ954
  Oleclumab
(MEDI9447)
Medimmune
(AstraZeneca)
Antibody N/A I.V NCT02503774 I Active, not recruiting Select advanced solid tumors YES Durvalumab
       NCT03736473 I Completed Advanced solid malignancies YES N/A
       NCT03773666 I Active, not recruiting Muscle-invasive bladder cancer N/A Durvalumab
       NCT03819465 I Not yet recruiting Previously untreated NSCLC N/A Durvalumab, ± CT
       NCT03381274 I/II Active, not recruiting NSCLC N/A Osimertinib or AZD4635
       NCT03611556 I/II Active, not recruiting metastatic pancreatic cancer N/A CT, ± durvalumab
       NCT03616886 I/II Active, not recruiting Previously untreated locally recurrent inoperable or metastatic TNBC N/A Durvalumab and CT
       NCT03742102 I/II Recruiting mTNBC N/A Durvalumab and CT
       NCT04068610 I/II Active, not recruiting MSS-CRC N/A Durvalumab, bevacizumab, and CT
       NCT03267589 II Completed Relapsed OC N/A Durvalumab, tremililumab, and MEDI0562
       NCT03334617 II Recruiting NSCLC N/A Durvalumab
       NCT03794544 II Completed Resectable NSCLC N/A Durvalumab
       NCT03822351 II Active, not recruiting NSCLC N/A Durvalumab
       NCT03833440 II Recruiting ICI-resistant NSCLC N/A Durvalumab
       NCT03875573 II Recruiting Luminal B breast cancer N/A SBRT and durvalumab
       NCT04145193 II Withdrawnc MSS-CRC N/A Durvalumab and CT
       NCT04262375 II Withdrawnd NSCLC, RCC N/A Durvalumab
       NCT04262388 II Withdrawne PDSC, NSCLC, HNSC N/A Durvalumab
       NCT04668300 II Recruiting Recurrent, refractory, or metastatic sarcoma N/A Durvalumab
       NCT04940286 II Recruiting Resectable/borderline resectable primary pancreatic cancer N/A Durvalumab and CT
       NCT05061550 II Not yet recruiting Resectable NSCLC N/A Durvalumab
       NCT05221840 III Recruiting Stage III unresectable NSCLC N/A Durvalumab
  ORIC-533 ORIC Pharmaceuticals Antagonist   Orally NCT05227144 I Recruiting Relapsed or refractory MM YES N/A
  Quemliclustat
(AB680)
Arcus Biosciences Antagonist   I.V NCT04104672 I Recruiting Gastrointestinal malignancies N/A CT or CT and zimberelimab
       NCT04381832 I/II Recruiting mCRPC N/A Etrumadenant and/or zimberelimab
       NCT04660812 I/II Recruiting mCRPC N/A AB928 and zimberelimab
  Sym024 Symphogen Antibody   I.V NCT04672434 I Recruiting Advanced solid tumors YES Sym021
  Uliledlimab
(TJ004309)
TRACON Pharmaceuticals Antibody   I.V NCT03835949 I Active, not recruiting Advanced or metastatic cancer N/A Atezolizumab
       NCT04869501 N/A No longer available Advanced or metastatic cancer N/A Atezolizumab
       NCT04322006 I/II Recruiting Advanced solid tumors YES Anti-PD1 antibody
       NCT05001347 II Recruiting OC and selected solid tumors YES N/A
  1. Term list: AK104 an anti-PD1/CTLA4 bispecific antibody, Atezolizumab an anti-PD-L1 antibody, Bevacizumab an anti-VEGF antibody, Budigalimab an anti-PD1 antibody, CT Chemotherapy, Daratumumab an anti-CD38 antibody, DFF332 a small molecule inhibitor for HIF2α, Domvanalimab an anti-TIGIT antibody, Durvalumab an anti-PD-L1 antibody, EOS-448 an anti-TIGIT antibody, HNSC Head and neck squamous cell carcinoma, ICI Immune checkpoint inhibitor, INCMGA00012 retifanlimab an anti-PD1 antibody, IPI-549 a PI3K-γ inhibitor, I.V. intravenously, LAG525 ieramilimab an anti-LAG3 antibody, mCRC metastatic colorectal cancer, mCRPC metastatic castration-resistant prostate cancer, MEDI0562 an anti-OX40 antibody, mGEC metastatic gastroesophageal cancer, MM multiple myeloma, mNSCLC metastatic non-small-cell lung carcinoma, mPDAC metastatic pancreatic ductal adenocarcinoma, MSS-CRC metastatic microsatellite-stable colorectal cancer, mTNBC metastatic TNBC, NHL Non-Hodgkin lymphoma, Nivolumab an anti-PD1 antibody, NP nanoparticle albumin-bound paclitaxel, NSCLC non-small-cell lung carcinoma, OC ovarian cancer, PC prostate cancer, PLD pegylated liposomal doxorubicin, RCC renal cell cancer, rHuPH20 recombinant human hyaluronidase PH20 enzyme, RT radiotherapy, SBRT stereotactic body radiotherapy, Sintilimab an anti-PD1 antibody, Spartalizumab Pembrolizumab an anti-PD1 antibody, PDR001 an anti-PD1 antibody, Sym021 an anti-PD1 antibody, TNBC triple-negative breast cancer, UC urothelial carcinoma, Zimberelimab an anti-PD1 antibody.
  2. aThe data did not support study endpoints
  3. bThe decision to discontinue the study was made based on the totality of the clinical, pharmacokinetic, and pharmacodynamic findings. No safety concerns were observed
  4. cStudy withdrawn prior to enrollment due to changing standard of care landscape
  5. dOverall clinical activity (ORR) for oleclumab + durvalumab is minimal across tumor types and does not support further evaluation of this doublet
  6. eOverall clinical activity (ORR) for oleclumab + durvalumab is minimal across tumor types and does not support further evaluation of this doublet