^
    14d
    PIONeeR: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (clinicaltrials.gov)
    P2, N=114, Active, not recruiting, Assistance Publique Hopitaux De Marseille | Recruiting --> Active, not recruiting | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Oct 2023 --> Oct 2024
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases • Immuno-oncology
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation • ALK rearrangement • ROS1 rearrangement
    |
    Imfinzi (durvalumab) • docetaxel • Orpathys (savolitinib) • ceralasertib (AZD6738) • oleclumab (MEDI9447) • monalizumab (IPH2201)
    23d
    BEGONIA: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=240, Recruiting, AstraZeneca | Trial completion date: Aug 2024 --> Nov 2024 | Trial primary completion date: Aug 2024 --> Nov 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • HER-2 expression • PD-L1 expression + HER-2 overexpression
    |
    Imfinzi (durvalumab) • paclitaxel • Enhertu (fam-trastuzumab deruxtecan-nxki) • Truqap (capivasertib) • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447)
    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)
    3ms
    MAGELLAN: A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC (clinicaltrials.gov)
    P1, N=175, Active, not recruiting, AstraZeneca | Trial completion date: May 2023 --> Mar 2026
    Trial completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR mutation • ALK fusion
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • pemetrexed • oleclumab (MEDI9447) • rilvegostomig (AZD2936) • volrustomig (MEDI5752) • danvatirsen (AZD9150)
    3ms
    NeoCOAST-2: Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=490, Recruiting, AstraZeneca | N=350 --> 490
    Enrollment change
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • paclitaxel • pemetrexed • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447) • volrustomig (MEDI5752) • AZD0171 • monalizumab (IPH2201)
    3ms
    Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial. (PubMed, Nat Med)
    A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)-ceralasertib (ATR kinase inhibitor), durvalumab-olaparib (PARP inhibitor), durvalumab-danvatirsen (STAT3 antisense oligonucleotide) or durvalumab-oleclumab (anti-CD73 monoclonal antibody). Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab-ceralasertib is under further investigation in immunotherapy-refractory NSCLC.ClinicalTrials.gov identifier: NCT03334617.
    P2 data • Journal • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    STK11 (Serine/threonine kinase 11) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    STK11 mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738) • oleclumab (MEDI9447) • danvatirsen (AZD9150)
    4ms
    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
    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)
    5ms
    COAST: Durvalumab Alone or in Combination With Novel Agents in Subjects With NSCLC (clinicaltrials.gov)
    P2, N=188, Completed, MedImmune LLC | Active, not recruiting --> Completed
    Trial completion
    |
    Imfinzi (durvalumab) • oleclumab (MEDI9447) • monalizumab (IPH2201)
    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)
    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
    Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase 2 NeoCOAST Platform Trial. (PubMed, Cancer Discov)
    Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti-PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). Safety profiles for the combinations were similar to that of durvalumab alone. Multiplatform immune profiling suggested improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune-cell activation.
    P2 data • Journal • PD(L)-1 Biomarker • IO biomarker • Immuno-oncology
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3) • KLRC1 (Killer Cell Lectin Like Receptor C1)
    |
    Imfinzi (durvalumab) • oleclumab (MEDI9447) • danvatirsen (AZD9150) • monalizumab (IPH2201)
    7ms
    NeoCOAST-2: Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=350, Recruiting, AstraZeneca | Trial completion date: Mar 2026 --> Dec 2028 | Trial primary completion date: Mar 2026 --> Dec 2028
    Trial completion date • Trial primary completion date • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • paclitaxel • pemetrexed • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447) • volrustomig (MEDI5752) • AZD0171 • monalizumab (IPH2201)
    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 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)
    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)
    8ms
    Bispecific antibody CD73xEGFR more selectively inhibits the CD73/adenosine immune checkpoint on cancer cells and concurrently counteracts pro-oncogenic activities of CD73 and EGFR. (PubMed, J Immunother Cancer)
    BsAb CD73xEGFR outperforms oleclumab as it inhibits the CD73/ADO immune checkpoint in an EGFR-directed manner and concurrently counteracts several oncogenic activities of EGFR and CD73. Therefore, bsAb CD73xEGFR may be of significant clinical potential for various forms of difficult-to-treat solid cancer types.
    Journal • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • CD8 (cluster of differentiation 8) • NT5E (5'-Nucleotidase Ecto)
    |
    CD73 overexpression • CD73 expression • NT5E overexpression
    |
    oleclumab (MEDI9447)
    10ms
    A Novel Bispecific Antibody for EpCAM-Directed Inhibition of the CD73/Adenosine Immune Checkpoint in Ovarian Cancer. (PubMed, Cancers (Basel))
    Thus far, conventional CD73-blocking antibodies such as oleclumab show limited clinical efficacy, probably due to the fact that it indiscriminately binds to and blocks CD73 on a massive surplus of normal cells...Additionally, treatment with bsAb CD73xEpCAM potently inhibited the proliferative capacity of OC cells and enhanced their sensitivity to cisplatin, doxorubicin, 5FU, and ionizing radiation. BsAb CD73xEpCAM may be useful in the development of tumor-directed immunotherapeutic approaches to overcome the CD73-mediated immunosuppression in patients with refractory OC.
    Journal
    |
    NT5E (5'-Nucleotidase Ecto)
    |
    CD73 expression • EPCAM expression
    |
    cisplatin • 5-fluorouracil • doxorubicin hydrochloride • oleclumab (MEDI9447)
    10ms
    D6070C00001: MEDI9447 Alone and in Combination With MEDI4736 in Adult Participants With Select Advanced Solid Tumors. (clinicaltrials.gov)
    P1, N=192, Completed, MedImmune LLC | Trial completion date: Jun 2023 --> Mar 2023 | Active, not recruiting --> Completed
    Trial completion • Trial completion date • Combination therapy • Metastases
    |
    Imfinzi (durvalumab) • oleclumab (MEDI9447)
    11ms
    Oleclumab (MEDI9447) Epidermal Growth Factor Receptor Mutant (EGFRm) Non-small Cell Lung Cancer (NSCLC) Novel Combination Study (clinicaltrials.gov)
    P1b/2, N=43, Active, not recruiting, MedImmune LLC | Trial completion date: Jan 2024 --> Sep 2024
    Trial completion date • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR T790M negative
    |
    Tagrisso (osimertinib) • oleclumab (MEDI9447) • imaradenant (AZD4635)
    11ms
    BEGONIA: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=203, Recruiting, AstraZeneca | Active, not recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • HER-2 expression • PD-L1 expression + HER-2 overexpression
    |
    Imfinzi (durvalumab) • paclitaxel • Enhertu (fam-trastuzumab deruxtecan-nxki) • Truqap (capivasertib) • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447)
    11ms
    SYNERGY: Paclitaxel + Carboplatin + Durvalumab With or Without Oleclumab for Previously Untreated Locally Recurrent Inoperable or Metastatic TNBC (clinicaltrials.gov)
    P1/2, N=129, Active, not recruiting, Jules Bordet Institute | Trial completion date: Oct 2023 --> Apr 2025 | Trial primary completion date: Jul 2023 --> Aug 2024
    Trial completion date • Trial primary completion date • IO biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • NT5E (5'-Nucleotidase Ecto)
    |
    PD-L1 expression • HER-2 positive • HR positive • HER-2 negative • ER negative • CD73 expression
    |
    carboplatin • Imfinzi (durvalumab) • paclitaxel • oleclumab (MEDI9447)
    11ms
    First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors. (PubMed, Cancer Immunol Immunother)
    Oleclumab ± durvalumab had a manageable safety profile, with pharmacodynamic activity reflecting oleclumab's mechanism of action. Evidence of antitumor activity was observed in tumor types that are generally immunotherapy resistant.
    P1 data • Clinical Trial,Phase I • Journal • Combination therapy • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • NT5E (5'-Nucleotidase Ecto)
    |
    EGFR mutation • CD73 expression
    |
    Imfinzi (durvalumab) • oleclumab (MEDI9447)
    12ms
    MAGELLAN: A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC (clinicaltrials.gov)
    P1, N=175, Active, not recruiting, AstraZeneca | N=258 --> 175 | Trial completion date: Mar 2026 --> May 2023 | Trial primary completion date: Mar 2026 --> May 2023
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR mutation • ALK fusion
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • pemetrexed • oleclumab (MEDI9447) • rilvegostomig (AZD2936) • volrustomig (MEDI5752) • danvatirsen (AZD9150)
    12ms
    An Open-label, Phase II Study of AZD4635 in Patients With Prostate Cancer (clinicaltrials.gov)
    P2, N=59, Completed, AstraZeneca | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Apr 2023
    Trial completion • Trial completion date
    |
    Imfinzi (durvalumab) • oleclumab (MEDI9447) • imaradenant (AZD4635)
    12ms
    A Phase 1 Clinical Study of AZD4635 in Patients With Advanced Solid Malignancies (clinicaltrials.gov)
    P1, N=313, Completed, AstraZeneca | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Mar 2023
    Trial completion • Trial completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR mutation • MSI-H/dMMR • ALK rearrangement
    |
    Imfinzi (durvalumab) • docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate • oleclumab (MEDI9447) • imaradenant (AZD4635)
    1year
    BEGONIA: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=240, Active, not recruiting, AstraZeneca | Trial completion date: Jun 2023 --> Aug 2024 | Trial primary completion date: Jun 2023 --> Aug 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • HER-2 expression • PD-L1 expression + HER-2 overexpression
    |
    Imfinzi (durvalumab) • paclitaxel • Enhertu (fam-trastuzumab deruxtecan-nxki) • Truqap (capivasertib) • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447)
    1year
    Tumor intrinsic and extrinsic functions of CD73 and the adenosine pathway in lung cancer. (PubMed, Front Immunol)
    CD73 is thought of mainly for its role as an immune modulator, however recent studies have demonstrated the tumor cell intrinsic properties of CD73 are potentially as important as its role in immune suppression. We also highlight the current understanding of this pathway in lung cancer, outline ongoing studies examining therapies in combination with adenosine pathway targeting, and discuss future prospects.
    Review • Journal • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • NT5E (5'-Nucleotidase Ecto)
    |
    KRAS mutation • EGFR mutation • CD73 expression
    |
    oleclumab (MEDI9447)
    1year
    NeoCOAST-2: Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=350, Recruiting, AstraZeneca | N=210 --> 350
    Enrollment change • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • paclitaxel • pemetrexed • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447) • volrustomig (MEDI5752) • AZD0171 • monalizumab (IPH2201)
    1year
    Oleclumab (MEDI9447) Epidermal Growth Factor Receptor Mutant (EGFRm) Non-small Cell Lung Cancer (NSCLC) Novel Combination Study (clinicaltrials.gov)
    P1b/2, N=43, Active, not recruiting, MedImmune LLC | Trial completion date: Dec 2022 --> Jan 2024
    Trial completion date • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR T790M negative
    |
    Tagrisso (osimertinib) • oleclumab (MEDI9447) • imaradenant (AZD4635)
    1year
    Phase 3 Study of Durvalumab Combined with Oleclumab or Monalizumab in Patients with Unresectable Stage III NSCLC (PACIFIC-9) (DGP 2023)
    Other secondary endpoints include ORR and DOR (RECIST v1.1; BICR), PROs, PD-L1 expression on tumor cells relative to efficacy outcomes, and safety/tolerability. Enrolment in PACIFIC-9 is ongoing.
    Clinical • P3 data • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • CD8 (cluster of differentiation 8) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • HLA-E (Major Histocompatibility Complex, Class I, E) • KLRC1 (Killer Cell Lectin Like Receptor C1)
    |
    PD-L1 expression • EGFR wild-type • ALK wild-type
    |
    Imfinzi (durvalumab) • oleclumab (MEDI9447) • monalizumab (IPH2201)
    1year
    BEGONIA: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=210, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2024 --> Jun 2023
    Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • HER-2 expression • PD-L1 expression + HER-2 overexpression
    |
    Imfinzi (durvalumab) • paclitaxel • Enhertu (fam-trastuzumab deruxtecan-nxki) • Truqap (capivasertib) • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447)
    1year
    D6070C00001: MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=190, Active, not recruiting, MedImmune LLC | Trial completion date: Jan 2023 --> Jun 2023
    Trial completion date • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation
    |
    Imfinzi (durvalumab) • oleclumab (MEDI9447)
    over1year
    BEGONIA: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=210, Active, not recruiting, AstraZeneca | Trial completion date: Feb 2023 --> Dec 2024 | Trial primary completion date: Feb 2023 --> Jun 2023
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 expression
    |
    Imfinzi (durvalumab) • paclitaxel • Enhertu (fam-trastuzumab deruxtecan-nxki) • Truqap (capivasertib) • datopotamab deruxtecan (DS-1062a) • oleclumab (MEDI9447)
    over1year
    CD73 Inhibitor Oleclumab Plus Osimertinib in Previously Treated Patients With Advanced T790M-Negative EGFRm Non-Small-Cell Lung Cancer: A Brief Report. (PubMed, J Thorac Oncol)
    Oleclumab plus osimertinib showed evidence of moderate activity with acceptable tolerability in previously treated patients with advanced EGFR-mutated NSCLC.
    Journal • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR T790M • CD73 overexpression • EGFR negative • EGFR T790M negative • CD73 expression
    |
    Tagrisso (osimertinib) • oleclumab (MEDI9447)
    over1year
    NeoCOAST-2: Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=210, Recruiting, AstraZeneca | N=140 --> 210
    Enrollment change • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • paclitaxel • pemetrexed • oleclumab (MEDI9447) • volrustomig (MEDI5752) • monalizumab (IPH2201)
    over1year
    Combination of IPH5201, a blocking antibody targeting the CD39 immunosuppressive pathway, with durvalumab and chemotherapies: Preclinical rationale (ESMO-IO 2022)
    Targeting the Ado pathway has recently been reported to improve Durvalumab (D) efficacy in early-stage NSCLC patients, through the use of Oleclumab, an anti-CD73 mAb...Finally, in vivo, in a mouse tumor model engrafted in huCD39KI mice, moIPH5201 improved the anti-tumor efficacy of gemcitabine and anti-PD-L1 combination. Conclusions IPH5201 was shown to block CD39 enzymatic activity, to lower Ado and increase ATP levels in the TME and finally to improve anti-tumor efficacy in preclinical models. Altogether, the expression profile of CD39 in early stage NSCLC and preclinical combination data support the clinical evaluation of IPH5201 in combination with D and CT in early stage NSCLC patients.
    Preclinical • PD(L)-1 Biomarker • IO biomarker
    |
    ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
    |
    PD-L1 expression • CD73 expression • ENTPD1 expression
    |
    Imfinzi (durvalumab) • gemcitabine • oleclumab (MEDI9447) • IPH5201
    over1year
    Neo-CheckRay: Neo-adjuvant Chemotherapy Combined With Stereotactic Body Radiotherapy to the Primary Tumour +/- Durvalumab, +/- Oleclumab in Luminal B Breast Cancer: (clinicaltrials.gov)
    P2; Trial completion date: Oct 2025 --> Jan 2026 | Trial primary completion date: Oct 2022 --> Dec 2023
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 positive • ER positive • HER-2 amplification • HER-2 negative
    |
    MammaPrint
    |
    Imfinzi (durvalumab) • doxorubicin hydrochloride • cyclophosphamide • oleclumab (MEDI9447)
    almost2years
    A Phase 1 Clinical Study of AZD4635 in Patients With Advanced Solid Malignancies (clinicaltrials.gov)
    P1, N=313, Active, not recruiting, AstraZeneca | Trial completion date: Jul 2022 --> Dec 2022
    Trial completion date
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR mutation • MSI-H/dMMR • ALK rearrangement
    |
    Imfinzi (durvalumab) • docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate • oleclumab (MEDI9447) • imaradenant (AZD4635)