Table 3.
Summary of clinical trials for CD73, A2AR, and A2BR in cancer.
| Adenosine pathway target | Drug(s) | Target(s) | Therapy modality (adenosine pathway) | Phase | Details | Disease | Status | ClinicalTrials.gov Identifier |
|---|---|---|---|---|---|---|---|---|
| CD73 | LY3475070 Pembrolizumab |
CD73PD-1 | LY3475070:CD73 SmallMolecule Inhibitor | Phase 1 | Cohort A: LY3475070 administered orallyCohort B: LY3475070 + Pembrolizumab administered IVCohort C1: LY3475070 + Pembrolizumab administered IVCohort C2 LY3475070 administered orallyCohort D1 LY3475070 + Pembrolizumab administered IVCohort D2: LY3475070 administered orallyCohort E: LY3475070 + Pembrolizumab administered IV | Advanced SolidMalignancies | Recruiting | NCT04148937 |
| Oleclumab (MEDI9447) Durvalumab (MEDI4736) |
CD73PD-L1 | Oleclumab: CD73 Humanized Monoclonal Antibody |
Phase 1 Phase 2 |
Phase I and Phase II Arm A: Paclitaxel, Carboplatin, Durvalumab, + OleclumabPhase II Arm B: Paclitaxel, Carboplatin, + Durvalumab | Triple NegativeBreast Cancer | Recruiting | NCT03616886 | |
| Oleclumab (MEDI9447) Durvalumab |
CD73PD-L1 | Oleclumab:CD73 HumanizedMonoclonalAntibody | Phase 2 | Experimental: Chemotherapy and radiation Experimental: Chemotherapy and pre-operative radiotherapy + Durvalumab Experimental: Chemotherapy and pre-operative radiotherapy + Durvalumab and Oleclumab |
Luminal B(Breast Cancer) | Recruiting | NCT03875573 | |
| Oleclumab(MEDI9447)Durvalumab | CD73PD-L1 | Oleclumab:CD73 HumanizedMonoclonalAntibody | Phase 1 | Experimental: Monotherapy, Oleclumab Experimental: Combination, Oleclumab and Durvalumab |
Solid Tumors | Active, not Recruiting |
NCT02503774 | |
| TJ004309Atezolizumab | CD73PD-L1 | TJ004309:CD73 HumanizedMonoclonalAntibody | Phase 1 | Dose escalated TJ004309 + Atezolizumab | Solid TumorsMetastatic Cancer | Recruiting | NCT03835949 | |
| Oleclumab (MEDI9447) Durvalumab AZD9150 AZD6738 Vistusertib Olaparib Trasutzumab Cediranib |
CD73 PD-L1 STAT3 ATR mTOR PARP HER2 VEGFR |
Oleclumab: CD73 Humanized Monoclonal Antibody |
Phase 2 | Experimental: Durvalumab + Olaparib Experimental: Durvalumab + AZD9150 Experimental: Durvalumab + AZD6738 Experimental: Durvalumab + Vistusertib Experimental: Durvalumab + Oleclumab Experimental: Durvalumab + Trastuzumab Experimental: Durvalumab + Cediranib |
Non-Small Cell Lung Cancer |
Recruiting | NCT03334617 | |
| Oleclumab (MEDI9447) Durvalumab Capivasertib Danvatirsen Paclitaxel |
CD73 PD-L1 AKT STAT3 Chemotherapy |
Oleclumab: CD73 Humanized Monoclonal Antibody |
Phase 1 Phase 2 |
Experimental: Durvalumab + Paclitaxel Experimental: Durvalumab + Paclitaxel + Capivasertib Experimental: Durvalumab + Paclitaxel + Danvatirsen Experimental: Durvalumab + Paclitaxel + Oleclumab |
Triple Negative Breast Cancer |
Recruiting | NCT03742102 | |
| Oleclumab (MEDI9447) Durvalumab Gemcitabine Nab-paclitaxel Oxaliplatin Leucovorin 5-FU |
CD73 PD-L1 Chemotherapy |
Oleclumab: CD73 Humanized Monoclonal Antibody |
Phase 1 Phase 2 |
Arm A1: Gemcitabine + Nab-paclitaxelArm A2: Oleclumab + Gemcitabine + Nab-paclitaxelArm A3: Oleclumab + Durvalumab + Gemcitabine/Nab-paclitaxelArm B1: Oxaliplatin + Leucovorin + 5-FU (mFOLFOX)Arm B2: Oleclumab + mFOLFOX | CarcinomaMetastatic PancreaticAdenocarcinoma | Active, notRecruiting | NCT03611556 | |
| Oleclumab (MEDI9447) Durvalumab |
CD73PD-L1 | Oleclumab:CD73 HumanizedMonoclonal Antibody | Phase 1 | Experimental: Monotherapy, Durvalumab Experimental: Combination, Durvalumab + Oleclumab |
Muscle InvasiveBladder Cancer | Recruiting | NCT03773666 | |
| BMS-986179 Nivolumab rHUPH20 |
CD73PD-1 Hyaluronidase |
Oleclumab: CD73 Humanized Monoclonal Antibody |
Phase 1 Phase 2 |
Arm A: Monotherapy, BMS-986179Arm B: Combination Therapy, BMS-986179 + NivolumabArm C: Combination Therapy, BMS-986179 + rHUPH20 | Malignant Solid Tumor |
Recruiting | NCT02754141 | |
| Oleclumab (MEDI9447) MEDI0562 Durvalumab Tremelilumab |
CD73 OX40 PD-L1 CTLA-4 |
Oleclumab: CD73 Humanized Monoclonal Antibody |
Phase 2 | Cohort A: Oleclumab + DurvalumabCohort B: MEDI0562 + DurvalumabCohort C: MEDI0562 + Tremelimumab | Ovarian Cancer | Recruiting | NCT03267589 | |
| CD73 A2AR | CPI-006 Ciforadenant (CPI-444) Pembrolizumab |
CD73 A2AR PD-1 |
CPI-006: CD73 Humanized Monoclonal Antibody Ciforadenant: A2AR Antagonist |
Phase 1 | Cohort 1a: (escalating doses) CPI-006Cohort 1b: (escalating doses) CPI-006 + CiforadenantCohort 1c: (escalating doses) CPI-006 + PembrolizumabCohort 2a: (selective dose) CPI-006Cohort 2b: (selective dose) CPI-006 + CiforadenantCohort 2c: (selective doses) CPI-006 + Pembrolizumab | Non-Small Cell Lung Cancer Renal Cell Cancer Colorectal Cancer Triple Negative Breast Cancer Cervical Cancer Ovarian Cancer Pancreatic Cancer Endometrial Cancer Sarcoma Squamous Cell Carcinoma of the Head and Neck Bladder Cancer Metastatic Castration Resistant Prostate Cancer Non-hodgkin Lymphoma |
Recruiting | NCT03454451 |
| Oleclumab (MEDI9447) AZD4635 Durvalumab |
CD73 A2AR PD-L1 |
Oleclumab: CD73 Humanized Monoclonal Antibody AZD4635: A2AR Antagonist |
Phase 2 | Module 1: Drug: AZD4635; Drug: DurvalumabModule 2: Drug: AZD4635; Drug: Oleclumab | Prostate Cancer Metastatic Castration-Resistant Prostate Cancer |
Recruiting | NCT04089553 | |
| Oleclumab (MEDI9447) AZD4635 Osimertinib |
CD73 A2AR EGFR |
Oleclumab: CD73 Humanized Monoclonal Antibody AZD4635: A2AR Antagonist |
Phase 1 Phase 2 |
Arm A: MEDI9447 + OsimertinibArm B: MEDI9447 + AZD4635 | Non-Small Cell Lung Cancer |
Recruiting | NCT03381274 | |
| NZV930NIR178PDR001 | CD73 A2AR PD-1 |
NZV930: CD73 Humanized Monoclonal Antibody NIR178: A2AR Antagonist |
Phase 1 | Experimental: NZV930 Experimental: NZV930 + PDR001 Experimental: NZV930 + NIR178 Experimental: NZV930, NIR178, PDR001 |
Non-small Cell Lung Cancer (NSCLC) Triple Negative Breast Cancer Pancreatic Ductal Adenocarcinoma Colorectal Cancer Microsatellite Stable Ovarian Cancer Renal Cell Carcinoma |
Recruiting | NCT03549000 | |
| Oleclumab (MEDI9447) AZD4635 Durvalumab Abiraterone Acetate Enzalutamide Docetaxel |
CD73 A2AR PD-L1 Hormone Therapy Chemotherapy |
Oleclumab: CD73 Humanized Monoclonal Antibody AZD4635: A2AR Antagonist |
Phase 1 | Experimental: Arm A: AZD4635 monotherapy as nanoparticle suspension 125 mg BID Experimental: Arm B: AZD4635 monotherapy as nanoparticle suspension 75 mg QD Experimental: Arm C: AZD4635 monotherapy as nanoparticle suspension 100 mg QD Experimental: Arm D: AZD4635 as nanoparticle suspension 75 mg QD plus Durvalumab Experimental: Arm E: AZD4635 as nanoparticle suspension 100 mg QD plus Durvalumab Experimental: Arm EA: AZD4635 as nanoparticle suspension plus Enzalutamide Experimental: Arm AA: AZD4635 as nanoparticle suspension plus Abiraterone Acetate Experimental: Arm F: AZD4635 as nanoparticle suspension plus Durvaluamb in patients post immunotherapy with non-small cell lung cancer Experimental: Arm G: AZD4635 monotherapy as nanoparticle suspension in patients post immunotherapy with non-small cell lung cancer Experimental: Arm H: AZD4635 monotherapy as nanoparticle suspension in patients post immunotherapy with other solid tumors Experimental: Arm I: AZD4635 as nanoparticle suspension plus Durvalumab in immunotherapy naïve patients with metastatic castration resistant prostate cancer Experimental: Arm J: AZD4635 as nanoparticle suspension plus Durvalumab in immunotherapy naïve patients with metastatic castration resistant prostate cancer |
Advanced Solid Malignancies Non-Small Cell Lung Cancer Metastatic Castrate-Resistant Prostate Carcinoma Colorectal Carcinoma |
Recruiting | NCT02740985 | |
| Experimental: Arm K: AZD4635 monotherapy as nanoparticle suspension in immunotherapy naïve patients with colorectal carcinoma Experimental: Arm KD: AZD4635 as nanoparticle suspension plus Durvalumab in immunotherapy-naïve patients with colorectal carcinoma Experimental: Arm L: AZD4635 monotherapy as nanoparticle suspension in immunotherapy naïve patients with other solid tumours Experimental: Arm CA: AZD4635 capsule formulation monotherapy 75 mg QD Experimental: Arm CB: AZD4635 capsule formulation 50 mg QD plus Durvalumab and Oleclumab Experimental: Arm CC: AZD4635 capsule formulation 50 mg QD plus Docetaxel |
||||||||
| A2AR | NIR178PDR001 | A2ARPD-1 | NIR178: A2AR Antagonist |
Phase 2 | Experimental (1): NIR178 + PDR001 Experimental (2): NIR178 BID Intermittent + PDR001 Experimental (3): Part 3, initiation of part 3 will depend on results from parts 1 and 2 Experimental (4): Japanese safety run-in part, two different dosing schedules of NIR178 will be explored |
Non-small Cell Lung Cancer Renal Cell Cancer Pancreatic Cancer Urothelial Cancer Head and Neck Cancer Diffused Large B Cell Lymphoma Microsatellite Stable Colon Cancer Triple Negative Breast Cancer Melanoma |
Recruiting | NCT03207867 |
| PBF-509PDR001 | A2ARPD-1 | PBF-509: A2AR Antagonist |
Phase 1 Phase 2 |
Drug: PBF-509_80 mgDrug: PBF-509_160 mgDrug: PBF-509_320 mgDrug: PBF-509_640 mgDrug: Combo PBF-509 (160 mg) + PDR001Drug: Combo PBF-509 (320 mg) + PDR001Drug: Combo PBF-509 (640 mg) + PDR001Drug: RP2D (PBF-509+PDR001)_immuno naïveDrug: Experimental: RP2D (PBF-509+PDR001)_immuno treated |
Non-small Cell Lung Cancer | Recruiting | NCT02403193 | |
| NIR178 Spartalizumab LAG525 Capmatinib MCS110 Canakinumab |
A2ARPD-1LAG-3c-MetM-CSFIL-1β | NIR178: A2AR Antagonist |
Phase 1 | Experimental: Spartalizumab + LAG525 + NIR178 Experimental: Spartalizumab + LAG525 + Capmatinib Experimental: spartalizumab + LAG525 + MCS110 Experimental: spartalizumab + LAG525 + Canakinumab |
Triple Negative Breast Cancer |
Recruiting | NCT03742349 | |
| Ciforadenant (CPI-444) Atezolizumab |
A2AR PD-L1 |
Ciforadenant: A2AR Antagonist |
Phase 1 | Experimental: Ciforadenant, 100 mg orally twice daily for the first 14 days of each 28-day cycle Experimental: Ciforadenant, 100 mg orally twice daily for 28 days of each 28-day cycle Experimental: Ciforadenant, 200 mg orally once daily for the first 14 days of each 28-day cycle Experimental: Ciforadenant + Atezolizumab Experimental: Ciforadenant, start with 150 mg orally twice daily for 28-day cycles; then, increase increments by 100 mg/day for 6 dose levels |
Non-Small Cell Lung Cancer Malignant Melanoma Renal Cell Cancer Triple Negative Breast Cancer Colorectal Cancer Bladder Cancer Metastatic Castration Resistant Prostate Cancer |
Recruiting | NCT02655822 | |
| Ciforadenant (CPI-444) Atezolizumab Cobimetinib RO6958688 Docetaxel Pemetrexed Carboplatin Gemcitabine Linagliptin Tocilizumab Ipatasertib Idasanutlin |
A2AR PD-L1 MEK CEA Chemotherapy IL-6R AKT MDM2 |
Ciforadenant: A2AR Antagonist |
Phase 1 Phase 2 |
Active Comparator: Stage 1: Cohort 1: Atezolizumab Experimental: Stage 1: Cohort 1: Atezolizumab + Cobimetinib Experimental: Stage 1: Cohort 1: Atezolizumab + RO6958688 Active Comparator: Stage 1: Cohort 2: Docetaxel Experimental: Stage 1: Cohort 2: Atezolizumab + Cobimetinib Experimental: Stage 1: Cohort 2: Atezolizumab + Ciforadenant Experimental: Stage 1: Cohort 2: Atezolizumab + RO6958688 Experimental: Stage 1: Cohort 2: Atezolizumab + Ipatasertib Experimental: Stage 1: Cohort 2: Idasanutlin + Docetaxel Experimental: Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin |
Carcinoma, Non-Small-Cell Lung | Recruiting | NCT03337698 | |
| A2AR A2BR | AB928 IPI-549 Doxorubicin Paclitaxel |
A2AR/A2BR PI3Kγ Chemotherapy |
AB928: Dual A2AR and A2BR Antagonist |
Phase 1 | Experimental: Dose Escalation-Arm A, AB928 + Pegylated Liposomal Doxorubicin Experimental: Dose Escalation-Arm B, AB928 + Nanoparticle Albumin-bound Paclitaxel Experimental: Dose Escalation-Arm C, AB928 + Pegylated Liposomal Doxorubicin + Nanoparticle Albumin-bound Paclitaxel Experimental: Dose Expansion-TNBC-Arm 1, dose from Arm A for AB928 + Pegylated Liposomal Doxorubicin Experimental: Dose Expansion-Ovarian-Arm 2, dose from Arm A for AB928 + Pegylated Liposomal Doxorubicin Experimental: Dose Expansion-TNBC-Arm 3, dose from Arm B for AB928 + Nanoparticle Albumin-bound Paclitaxel Experimental: Dose Expansion-TNBC-Arm 4, dose from Arm C for AB928 + IPI-549 + Pegylated Liposomal Doxorubicin |
Triple Negative Breast Cancer (TNBC) Ovarian Cancer |
Recruiting | NCT03719326 |
| AB928 mFOLFOX |
A2AR/A2BR Chemotherapy |
AB928: Dual A2AR and A2BR Antagonist |
Phase 1 | Experimental: Dose Escalation, AB928 + mFOLFOX Experimental: Dose Expansion-GE, dose from escalation for AB928 + mFOLFOX Experimental: Dose Expansion-CRC, dose from escalation for AB928 + mFOLFOX |
GastroEsophageal Cancer (GE) Colorectal Cancer (CRC) |
Recruiting | NCT03720678 | |
| AB928 Zimberelimab (AB122) |
A2AR/A2BR PD-1 |
AB928: Dual A2AR and A2BR Antagonist |
Phase 1 | Experimental: Dose Escalation, AB928 + fixed dose of Zimberelimab (AB122) Experimental: Dose Expansion-Renal Cell Carcinoma, recommended dose for expansion AB928 + Zimberelimab (AB122) Experimental: Dose Expansion, recommended dose for expansion AB928 + Zimberelimab (AB122) |
Non-small Cell Lung Cancer Squamous Cell Carcinoma of the Head and Neck Breast Cancer Colorectal Cancer Melanoma Bladder Cancer Ovarian Cancer Endometrial Cancer Merkel Cell Carcinoma GastroEsophageal Cancer Renal Cell Carcinoma Castration-resistant Prostate Cancer |
Recruiting | NCT03629756 | |
| AB928 AB154 Zimberelimab (AB122) |
A2AR/A2BR TIGIT PD-1 |
AB928: Dual A2AR and A2BR Antagonist |
Phase 2 | Experimental: Arm 1, Zimberelimab Experimental: Arm 2, AB154 + Zimberelimab Experimental: Arm 3, AB928 + AB154 + Zimberelimab |
Non-Small Cell Lung Cancer Non-squamous Non-Small Cell Lung Cancer Squamous Non-Small Cell Lung Cancer Lung Cancer |
Recruiting | NCT04262856 | |
| AB928 Zimberelimab (AB122) Carboplatin Pemetrexed Pembrolizumab |
A2AR/A2BR PD-1 Chemotherapy |
AB928: Dual A2AR and A2BR Antagonist |
Phase 1 | Experimental: Dose Escalation Arm A, AB928 + Carboplatin + Pemetrexed Experimental: Dose Escalation Arm B, AB928 + Carboplatin + Pemetrexed + Pembrolizumab Experimental: Dose Expansion Arm 1, recommended dose for expansion AB928 + Carboplatin + Pemetrexed in patients harboring sensitizing EGFR mutation Experimental: Dose Expansion Arm 2, recommended dose for expansion AB928 + Carboplatin + Pemetrexed + AB122 in patients harboring sensitizing EGFR mutation |
Non-Small Cell Lung Cancer Metastatic Non-Small Cell Lung Cancer Non-squamous Non-small Cell Neoplasm of Lung Sensitizing EGFR Gene Mutation |
Recruiting | NCT03846310 | |
| A2BR | PBF-1129 | A2BR | PBF-1129: A2BR Antagonist | Phase 1 | Experimental: PBF-1129_40 mg Experimental: PBF-1129_80 mg Experimental: PBF-1129_160 mg Experimental: PBF-1129_320 mg |
Non-Small Cell Lung Cancer | Recruiting | NCT03274479 |