Table 1.
Clinical trials (from NIH and EU registers) testing the potential use of purinergic targets in pancreatic and other cancers. Purpose of the studies varies from feasibility to safety, tolerability, pharmacokinetics, immunogenicity, and anti-tumor activity.
| Target | Drug +/− Combination Therapy or Outcome | Sponsor/Company | Cancer | Identifier | Study Phase |
|---|---|---|---|---|---|
| P2X7 | Biomarker, histopathologic response, analysis of inflammasome and polymorphisms, ointment with Ab against non-functional P2X7R | various | Inflammation, ovarian cancer, colon cancer, basal cell carcinoma, endometrial cancer, breast cancer | Ovarian Colon cancer NCT04122937 Breast cancer NCT01440413 |
Various stages |
| P2Y12 | Clopidogrel (P2Y12 antagonist) and chemotherapy | Assistance Publique-Hôpitaux de Paris | Treatment of locally advanced or metastatic pancreatic cancer | NCT02404363 | Phase III No results poster |
| A2A | NIR178 in (A2A antagonist) in combination with PDR001 (anti-PD-1 Ab) | Novartis Pharmaceuticals | Patients with solid tumors (including pancreatic cancer) and Non-Hodgkin Lymphoma | NCT03207867 | Phase II |
| CD39 | TTX-030 (anti-CD39 Ab) in combination with standard chemo- or immunotherapy | Tizona Therapeutics | Patients with advanced cancers | NCT04306900 | Phase I/Ib |
| SRF617(anti-CD39 Ab) | Surface Oncology | Patients with advanced solid tumors to improve immune response | NCT04336098 | Phase I | |
| TTX-030 (anti-CD39 Ab) +/− anti-PD1 immunotherapy | Tizona Therapeutics | Patients with advanced cancers | NCT03884556 | Phase I | |
| CD73 | AB680 (CD73 inhibitor) +/− AB122 (PD-1), nab-paclitaxel and gemcitabine | Arcus Bioscience | Advanced pancreatic cancer | NTC04104672 | Phase I |
| LY3475070 (CD73 inhibitor) +/− Pembrolizumab | Eli Lilly and Company | Patients with advanced solid malignancies including pancreatic cancer | NCT04148937 | Phase I | |
| MEDI9447 (oleclumab, anti-CF73 Ab) and MEDI4736 (durvalumab, anti PD-L1–PD-1 Ab) | MedImmune LLC | Patients with solid tumors including pancreatic cancer | NCT02503774 | Phase I | |
| BMS-986179 (anti-CD73 Ab) + Nivolumab (BMS- 936558, anti PD-1 Ab) | Bristol-Myers Squibb International Corporation | Patients with advanced tumors | EudraCT 2016-000603-91 | Phase I/IIa | |
| PD1 and CD73 | Durvalumab (MEDI4736, anti-PD-L1 Ab) + Oleclumab (MEDI9447, anti-CD73)i | University Health Network, Toronto and Astra Zeneca | Patients with PDAC and other cancers | NCT04262388 | Phase II |
| CD73 +/− A2A | NZV930 (anti-CD73 Ab) +/− PDR001 (anti-PD-1 Ab) +/− NIR178 (A2A antagonist) | Novartis Pharmaceuticals | Patients with advanced cancers including PDAC | NCT03549000 | Phase I/Ib |
| CD73 +/− A2A | CPI-006 (anti-CD73 Ab) +/− ciforadenant (oral A2A inhibitor) +/− pembrolizumab (anti-PD1 Ab) | Corvus Pharmaceuticals | Patients with selected advanced cancers including pancreatic cancer | NCT03454451 | Phase I/Ib |