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DRUG CLASS:

Adenosine A2A receptor antagonist

14d
ARC-4: A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer (clinicaltrials.gov)
P1, N=77, Completed, Arcus Biosciences, Inc. | Active, not recruiting --> Completed
Trial completion
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation
|
Keytruda (pembrolizumab) • carboplatin • pemetrexed • Yutuo (zimberelimab) • etrumadenant (AB928)
17d
Istradefylline for Parkinson Disease With Cognitive Impairment (clinicaltrials.gov)
P2, N=10, Active, not recruiting, Virginia Commonwealth University | Recruiting --> Active, not recruiting
Enrollment closed
17d
Evolution of myeloid-mediated immunotherapy resistance in prostate cancer. (PubMed, Nature)
Consistent with preclinical results, inhibition of A2ARs using ciforadenant in combination with programmed death 1 ligand 1 (PD-L1) blockade using atezolizumab induces clinical responses in patients with mCRPC. Moreover, inhibiting A2ARs results in a significant decrease in SPP1hi-TAM abundance in CRPC, indicating that this pathway is involved in both induction and downstream immunosuppression. Collectively, these findings establish SPP1hi-TAMs as key mediators of ICI resistance in mCRPC through adenosine signalling, emphasizing their importance as both a therapeutic target and a potential biomarker for predicting treatment efficacy.
Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • SPP1 (Secreted Phosphoprotein 1) • ADORA2A (Adenosine A2a Receptor)
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Tecentriq (atezolizumab) • ciforadenant (CPI-444)
1m
ARC-9: An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer. (clinicaltrials.gov)
P1/2, N=227, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Oct 2024 --> Jul 2025 | Trial primary completion date: Oct 2024 --> Jul 2025
Trial completion date • Trial primary completion date • Metastases
|
Avastin (bevacizumab) • 5-fluorouracil • Stivarga (regorafenib) • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)
1m
Adenosine 2A Receptor Antagonism and AIH in ALS (clinicaltrials.gov)
P1/2, N=40, Recruiting, University of Florida | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Oct 2024 --> Dec 2025
Trial completion date • Trial primary completion date
1m
A Study of ILB2109 in Patients With Advanced Solid Malignancies (clinicaltrials.gov)
P1, N=48, Active, not recruiting, Innolake Biopharm | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2024 --> Dec 2024
Enrollment closed • Trial primary completion date • Metastases
|
ILB-2109
2ms
The A2AR antagonist inupadenant promotes humoral responses in patients (ESMO-IO 2024)
These effects may play a substantial role in delaying progression in end-stage patients. Additional work is ongoing to demonstrate this new mechanism of action across clinical settings and patient populations.
Clinical
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CXCL13 (Chemokine (C-X-C motif) ligand 13) • ADORA2A (Adenosine A2a Receptor)
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CXCL13 expression
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nCounter® PanCancer IO 360™ Panel
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inupadenant (EOS-850)
3ms
Trial completion date
|
5-fluorouracil • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928)
3ms
New Formulation Study of Inupadenant (EOS100850) in Patients with Cancer (clinicaltrials.gov)
P1, N=57, Completed, iTeos Therapeutics | Recruiting --> Completed | Trial completion date: Nov 2023 --> May 2024 | Trial primary completion date: Oct 2023 --> May 2024
Trial completion • Trial completion date • Trial primary completion date • Metastases
|
inupadenant (EOS-850)
3ms
Keynote A54: First-in-Human Study of EOS100850 (Inupadenant) in Patients with Cancer (clinicaltrials.gov)
P1, N=119, Completed, iTeos Therapeutics | Active, not recruiting --> Completed | Trial primary completion date: Jun 2023 --> May 2024
Trial completion • Trial primary completion date • Combination therapy • Metastases
|
Keytruda (pembrolizumab) • carboplatin • paclitaxel • inupadenant (EOS-850)
3ms
ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov)
P1/2, N=173, Completed, Arcus Biosciences, Inc. | Active, not recruiting --> Completed
Trial completion • Combination therapy • Metastases
|
docetaxel • Xtandi (enzalutamide) • Yutuo (zimberelimab) • Trodelvy (sacituzumab govitecan-hziy) • etrumadenant (AB928) • quemliclustat (AB680)
4ms
Dual A2A/ A2B adenosine receptor antagonist M1069 counteracts immuno-suppressive mechanisms of adenosine and reduces tumor growth in vivo. (PubMed, Mol Cancer Ther)
In vivo, M1069 decreased tumor growth as a monotherapy and enhanced anti-tumor activity of bintrafusp alfa (BA) or cisplatin in syngeneic adenosinehi/CD73hi 4T1 breast tumor model, but not in the CD73 knockout (KO) 4T1 tumor model or in adenosinelow/CD73low MC38 murine colon carcinoma model. In summary, our dual A2A/A2B AR antagonist M1069 may counteract immune-suppressive mechanisms of high concentrations of adenosine in vitro and in vivo and enhance the anti-tumor activity of other agents, including BA and cisplatin.
Preclinical • Journal
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CD73 (5'-Nucleotidase Ecto) • IL2 (Interleukin 2) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • CXCL1 (Chemokine (C-X-C motif) ligand 1)
|
cisplatin • bintrafusp alfa (M7824) • M1069
5ms
ARC-9: An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer. (clinicaltrials.gov)
P1/2, N=227, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Jul 2024 --> Oct 2024 | Trial primary completion date: Jul 2024 --> Oct 2024
Trial completion date • Trial primary completion date • Metastases
|
Avastin (bevacizumab) • 5-fluorouracil • Stivarga (regorafenib) • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)
5ms
ARC-4: A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer (clinicaltrials.gov)
P1, N=77, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Aug 2024 --> Nov 2024 | Trial primary completion date: Aug 2024 --> Nov 2024
Trial completion date • Trial primary completion date
|
EGFR (Epidermal growth factor receptor)
|
Keytruda (pembrolizumab) • carboplatin • pemetrexed • Yutuo (zimberelimab) • etrumadenant (AB928)
6ms
Nociceptive adenosine A2A receptor on trigeminal nerves orchestrates CGRP release to regulate the progression of oral squamous cell carcinoma. (PubMed, Int J Oral Sci)
We further demonstrated the pro-tumor effect of CGRP by feeding mice with the clinically approved CGRP receptor antagonist rimegepant which inhibited the activation of ERK and YAP. Finally, we diminished the impact of CGRP on OSCC with istradefylline, a clinically available drug that targets neuronal A2AR. Therefore, we established trigeminal A2AR-mediated CGRP release as a promising druggable circuit in OSCC treatment.
Journal
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CD73 (5'-Nucleotidase Ecto) • ADORA2A (Adenosine A2a Receptor)
7ms
Discovery of a potent, selective, and tumor-suppressing antibody antagonist of adenosine A2A receptor. (PubMed, PLoS One)
Lead candidate TB206-001 displayed nanomolar binding of hA2AR-overexpressing HEK293 cells; cross-reactivity with mouse and cynomolgus A2AR but not human A1, A2B, or A3 receptors; functional antagonism of hA2AR in hA2AR-overexpressing HEK293 cells and peripheral blood mononuclear cells (PBMCs); and tumor-suppressing activity in colon tumor-bearing HuCD34-NCG mice. Given its therapeutic properties, TB206-001 is a good candidate for incorporation into next-generation bispecific immunotherapeutics.
Journal
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ADORA2A (Adenosine A2a Receptor)
7ms
A Study of ILB2109 and Toripalimab in Patients With Advanced Solid Malignancies (clinicaltrials.gov)
P1/2, N=200, Recruiting, Innolake Biopharm | Not yet recruiting --> Recruiting
Enrollment open
|
PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • CD68 (CD68 Molecule)
|
PD-L1 expression
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Loqtorzi (toripalimab-tpzi) • ILB-2109
7ms
A Study of ILB2109 in Patients With Advanced Solid Malignancies (clinicaltrials.gov)
P1, N=48, Recruiting, Innolake Biopharm | Trial completion date: Jan 2024 --> Feb 2025 | Trial primary completion date: Nov 2023 --> Aug 2024
Trial completion date • Trial primary completion date
|
ILB-2109
8ms
Trial primary completion date • Checkpoint inhibition • Metastases
|
Yutuo (zimberelimab) • etrumadenant (AB928) • quemliclustat (AB680)
8ms
ADPORT-601: TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors (clinicaltrials.gov)
P1/2, N=90, Active, not recruiting, Portage Biotech | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
|
PORT-6
9ms
Combination therapy • Enrollment closed
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
PD-L1 IHC 22C3 pharmDx
|
Yutuo (zimberelimab) • domvanalimab (AB154) • etrumadenant (AB928)
10ms
INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors (clinicaltrials.gov)
P1, N=54, Completed, Incyte Corporation | Active, not recruiting --> Completed
Trial completion • Combination therapy • Metastases
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CD8 (cluster of differentiation 8)
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Zynyz (retifanlimab-dlwr) • INCB106385
10ms
Enrollment closed • Metastases
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • ciforadenant (CPI-444)
10ms
Enrollment open
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • ciforadenant (CPI-444)
10ms
Effect of Istradefylline Treatment on Behavioral Measures of Apathy in Parkinson's Disease. (clinicaltrials.gov)
P=N/A, N=8, Terminated, Medical University of South Carolina | Active, not recruiting --> Terminated; recruitment issues
Trial termination
10ms
ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov)
P1/2, N=173, Active, not recruiting, Arcus Biosciences, Inc. | Phase classification: P1b/2 --> P1/2 | Trial completion date: Apr 2024 --> Aug 2024 | Trial primary completion date: Apr 2024 --> Aug 2024
Phase classification • Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
docetaxel • Xtandi (enzalutamide) • Yutuo (zimberelimab) • Trodelvy (sacituzumab govitecan-hziy) • etrumadenant (AB928) • quemliclustat (AB680)
10ms
An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer. (clinicaltrials.gov)
P1/2, N=227, Active, not recruiting, Arcus Biosciences, Inc. | Phase classification: P1b/2 --> P1/2 | Trial completion date: Jan 2024 --> Jul 2024 | Trial primary completion date: Jan 2024 --> Jul 2024
Phase classification • Trial completion date • Trial primary completion date • Metastases
|
Avastin (bevacizumab) • 5-fluorouracil • Stivarga (regorafenib) • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)
10ms
Phase 1b/2 Trial of Ipilimumab, Nivolumab, and Ciforadenant (Adenosine A2a Receptor Antagonist) in First-line Advanced Renal Cell Carcinoma. (clinicaltrials.gov)
P1/2, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2 | N=15 --> 24
Enrollment closed • Phase classification • Enrollment change • Metastases
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • ciforadenant (CPI-444)
11ms
A Phase 1 Study of YZJ-5053 Tablets in Participants With Advanced Solid Tumors (clinicaltrials.gov)
P1, N=157, Recruiting, Shanghai Haiyan Pharmaceutical Technology Co., Ltd.
New P1 trial • Metastases
1year
CPI-006 Alone and in Combination With Ciforadenant and With Pembrolizumab for Patients With Advanced Cancers (clinicaltrials.gov)
P1, N=117, Completed, Corvus Pharmaceuticals, Inc. | Active, not recruiting --> Completed | N=378 --> 117 | Trial completion date: Dec 2025 --> Feb 2023 | Trial primary completion date: Dec 2023 --> Dec 2022
Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
MSI (Microsatellite instability)
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Keytruda (pembrolizumab) • ciforadenant (CPI-444) • mupadolimab (CPI-006)
1year
Safety and pharmacokinetics of imaradenant (AZD4635) in Japanese patients with advanced solid malignancies: a phase I, open-label study. (PubMed, Cancer Chemother Pharmacol)
No new or unexpected safety concerns were identified, and imaradenant had an acceptable safety profile at both 50- and 75-mg QD.
PK/PD data • Journal • Metastases
|
ADORA2A (Adenosine A2a Receptor)
|
imaradenant (AZD4635)
1year
Istradefylline Effect Protocol on Parkinson's Disease Tremor (clinicaltrials.gov)
P4, N=27, Active, not recruiting, Georgetown University | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Sep 2023 --> Sep 2024
Enrollment closed • Trial completion date • Trial primary completion date
1year
Study to Assess EXS21546 in Combination in Patients With Advanced Solid Tumours (clinicaltrials.gov)
P1b/2a, N=6, Terminated, Exscientia AI Limited | N=110 --> 6 | Trial completion date: Mar 2026 --> Oct 2023 | Recruiting --> Terminated | Trial primary completion date: Sep 2025 --> Sep 2023; Emerging data demonstrates challenge for EXS21546 to reach suitable therapeutic index.
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Metastases
|
EXS21546
1year
ARC-7: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer (clinicaltrials.gov)
P2, N=151, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025
Trial completion date • Trial primary completion date • Combination therapy
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression • PD-L1 overexpression
|
Yutuo (zimberelimab) • domvanalimab (AB154) • etrumadenant (AB928)
1year
Enrollment change • Trial withdrawal • Combination therapy • IO biomarker • Metastases
|
cisplatin • Yutuo (zimberelimab) • etrumadenant (AB928)
1year
Trial primary completion date • Metastases
|
Avastin (bevacizumab) • 5-fluorouracil • Stivarga (regorafenib) • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)
1year
Phase 2 Study to evaluate the triplet combination of pemetrexed plus etrumadenant and zimberelimab in patients with previously treated advanced or MTAP-deficient metastatic urothelial carcinoma (mUC) (SITC 2023)
Exploratory objective is to evaluate progression-free and overall survival. Interim analysis for futility and safety occurs in cohorts of 5 patients and is performed based on Bayesian sequential methods.
Clinical • P2 data • PD(L)-1 Biomarker • IO biomarker • Metastases
|
CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
|
PD-L1 expression
|
pemetrexed • Yutuo (zimberelimab) • etrumadenant (AB928)
over1year
Enrollment open • Metastases
|
MTAP (Methylthioadenosine Phosphorylase) • IL17A (Interleukin 17A)
|
pemetrexed • Yutuo (zimberelimab) • etrumadenant (AB928)
over1year
New P1/2 trial • Metastases
|
Loqtorzi (toripalimab-tpzi) • ILB-2109
over1year
ARC-4: A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer (clinicaltrials.gov)
P1, N=77, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Jul 2023 --> Aug 2024 | Trial primary completion date: Jul 2023 --> Aug 2024
Trial completion date • Trial primary completion date
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation
|
Keytruda (pembrolizumab) • carboplatin • pemetrexed • Yutuo (zimberelimab) • etrumadenant (AB928)
over1year
Enrollment open • Checkpoint inhibition • Metastases
|
Yutuo (zimberelimab) • etrumadenant (AB928) • quemliclustat (AB680)