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    DRUG:

    ciforadenant (CPI-444)

    i
    Other names: CPI-444, CPI 444, CPI444, V 81444, V81444, V-81444
    Associations

    News

    Trials
    Company:
    Angel Pharma, Corvus Pharma, Ligand
    Drug class:
    Adenosine A2A receptor antagonist
    Related drugs:
    Associations

    News

    Trials
    18d
    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
    |
    CD8 (cluster of differentiation 8) • SPP1 (Secreted Phosphoprotein 1) • ADORA2A (Adenosine A2a Receptor)
    |
    Tecentriq (atezolizumab) • ciforadenant (CPI-444)
    7ms
    Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
    P1/2, N=675, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Jun 2026 --> Sep 2025 | Recruiting --> Active, not recruiting | Trial completion date: Sep 2027 --> Nov 2026
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • tiragolumab (RG6058) • Repatha (evolocumab) • camonsertib (RP-3500) • cibisatamab (RG7802) • ciforadenant (CPI-444) • zanzalintinib (XL092)
    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
    Enrollment closed • Metastases
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • ciforadenant (CPI-444)
    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, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting
    Enrollment open
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • ciforadenant (CPI-444)
    10ms
    Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
    P1/2, N=675, Recruiting, Hoffmann-La Roche | N=470 --> 675 | Trial completion date: Nov 2026 --> Sep 2027 | Trial primary completion date: Aug 2025 --> Jun 2026
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • tiragolumab (RG6058) • camonsertib (RP-3500) • cibisatamab (RG7802) • ciforadenant (CPI-444) • zanzalintinib (XL092)
    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)
    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)
    |
    Keytruda (pembrolizumab) • ciforadenant (CPI-444) • mupadolimab (CPI-006)
    over1year
    Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
    P1/2, N=470, Recruiting, Hoffmann-La Roche | Trial completion date: Aug 2025 --> Nov 2026 | Trial primary completion date: Apr 2024 --> Aug 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • tiragolumab (RG6058) • Repatha (evolocumab) • camonsertib (RP-3500) • cibisatamab (RG7802) • ciforadenant (CPI-444) • zanzalintinib (XL092)
    over1year
    Phase 1b/2 trial of Ipilimumab, Nivolumab, and Ciforadenant (INC) (adenosine A2a receptor antagonist) in first-line advanced renal cell carcinoma (KCRS 2023)
    No abstract available
    Clinical • P1/2 data • Metastases
    |
    ADORA2A (Adenosine A2a Receptor)
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • ciforadenant (CPI-444)
    2years
    Phase 1b/2 trial of Ipilimumab, Nivolumab, and Ciforadenant (INC) (adenosine A2a receptor antagonist) in first-line advanced renal cell carcinoma (KCRS 2022)
    In the same study, the addition of ciforadenant to PD-L1 blockade with atezolizumab was shown to be safe and demonstrate activity with mPFS of 5.8 months and OS probability at 25 months of 90%. Exploratory objectives include assessing gene expression signatures and pharmacodynamic parameters with outcome. Results n/a Conclusions n/a Keywords: adenosine, metabolism, first-line, immunotherapy
    Clinical • P1/2 data • PD(L)-1 Biomarker • IO biomarker
    |
    CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • ADORA2A (Adenosine A2a Receptor) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
    |
    Opdivo (nivolumab) • Tecentriq (atezolizumab) • Yervoy (ipilimumab) • ciforadenant (CPI-444)
    over2years
    Combinatorial delivery of CPI444 and vatalanib loaded on PEGylated graphene oxide as an effective nanoformulation to target glioblastoma multiforme: In vitro evaluation. (PubMed, Front Oncol)
    Ultimately, GBM U87 cells assumed programmed cell death at a very low concentration due to nanocarrier-mediated drug delivery along with the chosen combination of drugs. Together, this study demonstrated the advantage of GO-PEG mediated combined delivery of CPI444 and vatalanib drugs with increased permeability, a three-pronged combinatorial strategy toward effective GBM treatment.
    Preclinical • Journal
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD24 (CD24 Molecule) • POU5F1 (POU Class 5 Homeobox 1) • NANOG (Nanog Homeobox)
    |
    CD24 expression
    |
    ciforadenant (CPI-444) • vatalanib (PTK787)
    over2years
    CPI-006 Alone and in Combination With Ciforadenant and With Pembrolizumab for Patients With Advanced Cancers (clinicaltrials.gov)
    P1, N=378, Active, not recruiting, Corvus Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy
    |
    MSI (Microsatellite instability)
    |
    Keytruda (pembrolizumab) • ciforadenant (CPI-444) • mupadolimab (CPI-006)
    over2years
    CPI-006 Alone and in Combination With Ciforadenant and With Pembrolizumab for Patients With Advanced Cancers (clinicaltrials.gov)
    P1, N=378, Recruiting, Corvus Pharmaceuticals, Inc. | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Mar 2022 --> Dec 2023
    Trial completion date • Trial primary completion date • Combination therapy
    |
    MSI (Microsatellite instability)
    |
    Keytruda (pembrolizumab) • ciforadenant (CPI-444) • mupadolimab (CPI-006)
    almost3years
    Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
    P1/2, N=435, Recruiting, Hoffmann-La Roche | Trial completion date: Nov 2023 --> Aug 2025 | Trial primary completion date: Feb 2022 --> Apr 2024
    Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • Repatha (evolocumab) • cibisatamab (RG7802) • ciforadenant (CPI-444)
    almost3years
    Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
    P1/2; N=435; Recruiting; Sponsor: Hoffmann-La Roche; Trial primary completion date: Jun 2022 --> Feb 2022
    Trial primary completion date • Clinical
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • Repatha (evolocumab) • cibisatamab (RG7802) • ciforadenant (CPI-444)
    over3years
    Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
    P1/2, N=435, Recruiting, Hoffmann-La Roche | Trial completion date: Feb 2024 --> Nov 2023
    Clinical • Trial completion date
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • Repatha (evolocumab) • cibisatamab (RG7802) • ciforadenant (CPI-444)
    over3years
    Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
    P1/2, N=435, Recruiting, Hoffmann-La Roche | Trial completion date: Nov 2023 --> Feb 2024 | Trial primary completion date: Feb 2022 --> Jun 2022
    Clinical • Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • Repatha (evolocumab) • cibisatamab (RG7802) • ciforadenant (CPI-444)
    almost4years
    Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
    P1/2, N=380, Recruiting, Hoffmann-La Roche | Trial completion date: Apr 2022 --> Nov 2023
    Clinical • Trial completion date
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • Repatha (evolocumab) • cibisatamab (RG7802) • ciforadenant (CPI-444)
    over4years
    [VIRTUAL] CD68+ tumor-associated myeloid cells as the target of adenosine-induced gene products and predictor of response to adenosine blockade with ciforadenant (cifo) in renal cell cancer (RCC). (ASCO 2020)
    We described an adenosine induced gene expression signature (AS, Fong, Cancer Disc 2020) that correlates with response to therapy with cifo, an adenosine A2A receptor antagonist, as monotherapy or in combination with atezolizumab in refractory RCC. Adenosine immunosuppression is mediated by M2 macrophages, which can be reversed by cifo. Enumerating tumor infiltrating CD68+ cells may be a valuable biomarker for identifying pts that will respond to adenosine blockade. Research Funding: Corvus Pharmaceuticals
    PD(L)-1 Biomarker • IO biomarker
    |
    CD163 (CD163 Molecule) • CXCR2 (Chemokine (C-X-C motif) receptor 2)
    |
    PD-L1 expression
    |
    Tecentriq (atezolizumab) • ciforadenant (CPI-444)
    over5years
    Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
    P1/2; N=410 --> 250
    Enrollment change • Clinical
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • Repatha (evolocumab) • cibisatamab (RG7802) • ciforadenant (CPI-444)
    almost6years
    Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
    P1/2; N=292 --> 410
    Enrollment change • Clinical
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • Repatha (evolocumab) • cibisatamab (RG7802) • ciforadenant (CPI-444)