^
    4d
    Biomimetic nanodrug blocks CD73 to inhibit adenosine and boosts antitumor immune response synergically with photothermal stimulation. (PubMed, J Nanobiotechnology)
    The nanodrug, named as AptEM@CBA, is constructed by encapsulation of photothermal agent black phosphorus quantum dots (BPQDs) and selective CD73 inhibitor α, β-Methyleneadenosine 5'-diphosphate (AMPCP) in chitosan nanogels, which are further covered with aptamer AS1411 modified erythrocyte membrane (EM) for biomimetic camouflage...Meanwhile, the release of AMPCP suppress the adenosine generation via CD73 blockade, alleviating the impairment of adenosine to dendritic cells and suppressing regulatory T cells, synergically stimulate the activity of T cells. The combination of CD73 blockade with PTT, not only suppresses the growth of primary implanted tumors, but also boosts strong antitumor immunity to inhibit the growth of distal tumors, providing good potential for tumor photoimmunotherapy.
    Journal
    |
    CD73 (5'-Nucleotidase Ecto)
    |
    CD73 elevation
    |
    QN-165
    10d
    Study of AK119 in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=16, Completed, Akeso | Recruiting --> Completed | N=48 --> 16
    Trial completion • Enrollment change • Metastases
    |
    drebuxelimab (AK119)
    11d
    Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov)
    P1, N=48, Active, not recruiting, Symphogen A/S | N=100 --> 48
    Enrollment change • Combination therapy • Metastases
    |
    MSI (Microsatellite instability)
    |
    MSI-H/dMMR
    |
    S95024 • Sym021
    16d
    Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov)
    P1, N=100, Active, not recruiting, Symphogen A/S | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2024 --> Dec 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    MSI (Microsatellite instability)
    |
    MSI-H/dMMR
    |
    S95024 • Sym021
    21d
    A novel small molecule inhibitor of CD73 triggers immune-mediated multiple myeloma cell death. (PubMed, Blood Cancer J)
    No abstract available
    Journal
    |
    CD73 (5'-Nucleotidase Ecto)
    |
    ORIC-533
    27d
    ARC-8: A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies (clinicaltrials.gov)
    P1, N=165, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Jun 2024 --> May 2027 | Trial primary completion date: Jun 2024 --> May 2027
    Trial completion date • Trial primary completion date • Combination therapy
    |
    CD73 (5'-Nucleotidase Ecto)
    |
    gemcitabine • albumin-bound paclitaxel • Yutuo (zimberelimab) • quemliclustat (AB680)
    1m
    EDGE-Gastric: A Safety and Efficacy Study of Treatment Combinations With and Without Chemotherapy in Adult Participants With Advanced Upper Gastrointestinal Tract Malignancies (clinicaltrials.gov)
    P2, N=360, Recruiting, Arcus Biosciences, Inc. | N=200 --> 360 | Trial completion date: Nov 2025 --> Jun 2027 | Trial primary completion date: Sep 2025 --> Sep 2026
    Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    5-fluorouracil • oxaliplatin • Yutuo (zimberelimab) • leucovorin calcium • domvanalimab (AB154) • quemliclustat (AB680)
    1m
    Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases (clinicaltrials.gov)
    P2, N=24, Recruiting, Weill Medical College of Cornell University | Not yet recruiting --> Recruiting
    Enrollment open
    |
    CD8 (cluster of differentiation 8)
    |
    balstilimab (AGEN2034) • botensilimab (AGEN1181) • dalutrafusp alfa (AGEN1423)
    1m
    CHANCES: A Phase 1 First-In-Human Study of the Anti-CD73 IPH5301 Alone or in Combination With Chemotherapy and Trastuzumab in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=27, Recruiting, Institut Paoli-Calmettes | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Mar 2024 --> Mar 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 positive • HER-2 overexpression
    |
    Herceptin (trastuzumab) • paclitaxel • IPH5301
    2ms
    Neo-CheckRay: Neo-adjuvant Chemotherapy Combined With Stereotactic Body Radiotherapy to the Primary Tumour +/- Durvalumab, +/- Oleclumab in Luminal B Breast Cancer: (clinicaltrials.gov)
    P2; Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> Sep 2029 | Trial primary completion date: Jan 2024 --> Sep 2024
    Trial completion date • Trial primary completion date • Enrollment closed
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    MammaPrint
    |
    Imfinzi (durvalumab) • doxorubicin hydrochloride • cyclophosphamide • oleclumab (MEDI9447)
    2ms
    Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases (clinicaltrials.gov)
    P2, N=24, Not yet recruiting, Weill Medical College of Cornell University
    New P2 trial
    |
    CD8 (cluster of differentiation 8)
    |
    balstilimab (AGEN2034) • botensilimab (AGEN1181) • dalutrafusp alfa (AGEN1423)
    2ms
    AIRPanc: Combination Therapy in Patients With Localized Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov)
    P2, N=60, Recruiting, Gulam Manji | Initiation date: Oct 2023 --> Jun 2024
    Trial initiation date • Combination therapy • Checkpoint inhibition • Checkpoint block • Metastases
    |
    5-fluorouracil • oxaliplatin • irinotecan • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)
    3ms
    Zimberelimab and Quemliclustat in Combination With Chemotherapy for the Treatment of Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov)
    P1/2, N=56, Suspended, Jonsson Comprehensive Cancer Center | Recruiting --> Suspended
    Trial suspension • Combination therapy • Metastases
    |
    oxaliplatin • irinotecan • Yutuo (zimberelimab) • leucovorin calcium • fluorouracil topical • quemliclustat (AB680)
    3ms
    AGEN1423 Plus Balstilimab With or Without Chemo in Pancreatic Cancer (clinicaltrials.gov)
    P2, N=24, Not yet recruiting, Bruno Bockorny | Trial completion date: May 2025 --> May 2027 | Trial primary completion date: May 2024 --> May 2026
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    gemcitabine • albumin-bound paclitaxel • balstilimab (AGEN2034) • dalutrafusp alfa (AGEN1423)
    3ms
    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)
    3ms
    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 capsule) • Yutuo (zimberelimab) • Trodelvy (sacituzumab govitecan-hziy) • etrumadenant (AB928) • quemliclustat (AB680)
    3ms
    Dose Escalation/Expansion Study of PT199 (an Anti-CD73 mAb) Administered Alone and in Combination With a PD-1 Inhibitor (the MORNINGSTAR Study) (clinicaltrials.gov)
    P1, N=40, Recruiting, Phanes Therapeutics | Trial completion date: Jan 2024 --> Aug 2025 | Trial primary completion date: Nov 2023 --> Dec 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    CD73 (5'-Nucleotidase Ecto)
    |
    PD-L1 expression
    |
    Tevimbra (tislelizumab)
    3ms
    Oleclumab (MEDI9447) Epidermal Growth Factor Receptor Mutant (EGFRm) Non-small Cell Lung Cancer (NSCLC) Novel Combination Study (clinicaltrials.gov)
    P1/2, N=43, Active, not recruiting, MedImmune LLC | Phase classification: P1b/2 --> P1/2 | Trial completion date: Sep 2024 --> Jan 2025
    Phase classification • Trial completion date • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR T790M negative
    |
    Tagrisso (osimertinib) • oleclumab (MEDI9447) • imaradenant (AZD4635)
    4ms
    Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov)
    P1, N=100, Active, not recruiting, Symphogen A/S | Trial completion date: Dec 2023 --> Jul 2024 | Trial primary completion date: Dec 2023 --> Jul 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    MSI (Microsatellite instability)
    |
    MSI-H/dMMR
    |
    S95024 • Sym021
    4ms
    A Study of AK131 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=130, Recruiting, Akeso | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    4ms
    Efficacy and pharmacodynamic effect of anti-CD73 and anti-PD-L1 monoclonal antibodies in combination with cytotoxic therapy: observations from mouse tumor models. (PubMed, Cancer Biol Ther)
    Using a murine monoclonal antibody surrogate of Oleclumab, we investigated the effect of CD73 inhibition in concert with cytotoxic therapies (chemotherapies as well as fractionated radiotherapy) and PD-L1 blockade...This therapeutic outcome was in part driven by cytotoxic CD8 T-cells, as evidenced by the detrimental effect of CD8 depleting antibody treatment of MCA205 tumor bearing mice treated with anti-CD73, anti-PD-L1 and 5-Fluorouracil+Oxaliplatin (5FU+OHP)...Inclusion of comparator groups representing the various components of the combination allowed deconvolution of contribution of the individual therapeutic elements; highlighting specific effects mediated by the anti-CD73 antibody with respect to immune-cell representation, chemotaxis and myeloid biology. These pre-clinical data reflect complementarity of adenosine blockade with cytotoxic therapy, and T-cell checkpoint inhibition, and provides new mechanistic insights in support of combination therapy.
    PK/PD data • Preclinical • Journal • Combination therapy • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • NT5E (5'-Nucleotidase Ecto)
    |
    5-fluorouracil • oxaliplatin • oleclumab (MEDI9447)
    4ms
    Testing the Safety of Adding Either Monalizumab (IPH2201) or Oleclumab (MEDI9447) to Durvalumab (MEDI4736) Plus Standard Radiation Therapy for Locally Advanced Non-small Cell Lung Cancer (NSCLC), The ARCHON-1 Trial (clinicaltrials.gov)
    P1; Suspended --> Recruiting
    Enrollment open • Metastases
    |
    PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
    |
    PD-L1 expression • PD-L1 overexpression
    |
    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay
    |
    Imfinzi (durvalumab) • oleclumab (MEDI9447) • monalizumab (IPH2201)
    4ms
    DORA: Durvalumab and Oleclumab in Resectable PDAC (clinicaltrials.gov)
    P2, N=22, Recruiting, University Health Network, Toronto | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Imfinzi (durvalumab) • oleclumab (MEDI9447)
    4ms
    Testing the Safety of Adding Either Monalizumab (IPH2201) or Oleclumab (MEDI9447) to Durvalumab (MEDI4736) Plus Standard Radiation Therapy for Locally Advanced Non-small Cell Lung Cancer (NSCLC), The ARCHON-1 Trial (clinicaltrials.gov)
    P1; N=24 --> 48
    Enrollment change • Metastases
    |
    PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
    |
    PD-L1 expression • PD-L1 overexpression
    |
    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay
    |
    Imfinzi (durvalumab) • oleclumab (MEDI9447) • monalizumab (IPH2201)
    4ms
    Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers (clinicaltrials.gov)
    P2, N=39, Recruiting, Nataliya Uboha | Trial completion date: Dec 2024 --> Jul 2025 | Trial primary completion date: Jun 2024 --> Jan 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    cisplatin • gemcitabine • Yutuo (zimberelimab) • quemliclustat (AB680)
    4ms
    Study of INCA 0186 in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=57, Active, not recruiting, Incyte Corporation | Trial completion date: Jan 2024 --> Jun 2025 | Trial primary completion date: Jan 2024 --> Jun 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    CD8 (cluster of differentiation 8)
    |
    Zynyz (retifanlimab-dlwr) • INCA00186 • INCB106385
    5ms
    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)
    5ms
    Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers (clinicaltrials.gov)
    P2, N=39, Recruiting, Nataliya Uboha | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    cisplatin • gemcitabine • Yutuo (zimberelimab) • quemliclustat (AB680)
    5ms
    Small molecular CD73 inhibitors: Recent progress and future perspectives. (PubMed, Eur J Med Chem)
    Therefore, attenuating or completely removing adenosine-mediated immunosuppression in the tumor microenvironment by inhibiting CD73 is a promising approach in the treatment of solid tumors. This paper focuses on the research progress of CD73 enzyme and CD73 small molecule inhibitors, and is expected to provide some insights into the development of small-molecule antitumor drugs targeting CD73.
    Review • Journal
    |
    CD73 (5'-Nucleotidase Ecto)
    5ms
    A Study of AK131 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=130, Not yet recruiting, Akeso
    New P1 trial
    5ms
    First-in-human study of SBRT and adenosine pathway blockade to potentiate the benefit of immunochemotherapy in early-stage luminal B breast cancer: results of the safety run-in phase of the Neo-CheckRay trial. (PubMed, J Immunother Cancer)
    P2; This novel treatment combination was considered safe and is worth further investigation in a randomized phase II trial.
    Journal • P1 data
    |
    PD-L1 (Programmed death ligand 1)
    |
    MammaPrint
    |
    Imfinzi (durvalumab) • paclitaxel • doxorubicin hydrochloride • cyclophosphamide • oleclumab (MEDI9447)
    5ms
    Phase 1b/2 Platform Study of Select Immunotherapy Combinations in Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
    P1/2, N=176, Not yet recruiting, Servier Bio-Innovation LLC
    New P1/2 trial
    |
    PD-L1 (Programmed death ligand 1)
    |
    Libtayo (cemiplimab-rwlc) • S95029
    5ms
    ARC-8: Phase 1/1b randomized study of quemliclustat + gemcitabine/nab-paclitaxel ± zimberelimab in patients with treatment-naive metastatic pancreatic adenocarcinoma. (ASCO-GI 2024)
    Results from ARC-8 demonstrate the addition of Q 100 mg ± Z to G/nP was safe and tolerable, with no significant added toxicity to GnP. Modulation of eADO with Q may confer benefit beyond radiographic measures of disease. The OS is promising and supports further development of Q in mPDAC.
    Clinical • P1 data • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    CD73 (5'-Nucleotidase Ecto) • NT5E (5'-Nucleotidase Ecto)
    |
    CD73 elevation • CD73 expression
    |
    gemcitabine • albumin-bound paclitaxel • Yutuo (zimberelimab) • quemliclustat (AB680)
    5ms
    Tumor Microenvironment Responsive CD8 T Cells and Myeloid-Derived Suppressor Cells to Trigger CD73 Inhibitor AB680-Based Synergistic Therapy for Pancreatic Cancer. (PubMed, Adv Sci (Weinh))
    AB680, an exceptionally potent and selective inhibitor of CD73, is administered in an early clinical trial, in conjunction with gemcitabine and anti-PD-1 therapy, for the treatment of PDAC. Finally, the supplementation of a CXCR2 inhibitor is validated to further enhance the therapeutic efficacy when combined with AB680 plus PD-1 inhibitor. These findings systematically demonstrate the efficacy and immunoregulatory mechanism of AB680, providing a novel, efficient, and promising immunotherapeutic combination strategy for PDAC.
    Journal
    |
    CD8 (cluster of differentiation 8) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • CXCR2 (Chemokine (C-X-C motif) receptor 2)
    |
    gemcitabine • quemliclustat (AB680)
    6ms
    Study of Dalutrafusp Alfa (Formerly GS-1423) in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=22, Terminated, Gilead Sciences | Phase classification: P1a/1b --> P1
    Phase classification • Combination therapy • Metastases
    |
    5-fluorouracil • oxaliplatin • leucovorin calcium • dalutrafusp alfa (AGEN1423)
    6ms
    COLUMBIA 1: COLUMBIA-1: Novel Oncology Therapies in Combination With Chemotherapy and Bevacizumab as First- Line Therapy in MSS-CRC (clinicaltrials.gov)
    P1/2, N=61, Terminated, MedImmune LLC | Phase classification: P1b/2 --> P1/2 | Completed --> Terminated; On 17 February 2022, the decision was made to terminate the clinical study because superior efficacy was not observed for the novel study drug combinations under investigation.
    Phase classification • Trial termination • Combination therapy • Metastases
    |
    Avastin (bevacizumab) • Imfinzi (durvalumab) • 5-fluorouracil • oxaliplatin • leucovorin calcium • oleclumab (MEDI9447)
    6ms
    Gemcitabine, Nab-paclitaxel, Durvalumab, and Oleclumab Before Surgery for the Treatment of in Resectable/Borderline Resectable Primary Pancreatic Cancer (clinicaltrials.gov)
    P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025
    Trial completion date • Trial primary completion date • Surgery
    |
    Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • oleclumab (MEDI9447)
    6ms
    ARC-8: A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies (clinicaltrials.gov)
    P1, N=165, Active, not recruiting, Arcus Biosciences, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Jun 2024 | Trial primary completion date: Jan 2024 --> Jun 2024
    Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
    |
    gemcitabine • albumin-bound paclitaxel • Yutuo (zimberelimab) • quemliclustat (AB680)
    6ms
    A Study of HB0045 Injection in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=71, Recruiting, Shanghai Huaota Biopharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    MSI (Microsatellite instability) • CD4 (CD4 Molecule)
    |
    HB0045
    7ms
    Gemcitabine, Nab-paclitaxel, Durvalumab, and Oleclumab Before Surgery for the Treatment of in Resectable/Borderline Resectable Primary Pancreatic Cancer (clinicaltrials.gov)
    P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Oct 2023 --> Oct 2024
    Trial primary completion date • Surgery
    |
    Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • oleclumab (MEDI9447)