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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