表 1.
A2AR拮抗剂临床试验概览
Clinical trials related to A2AR antagonists
| Drugs | Company | ClinicalTrials.gov Number | Study phase | Combination | Cancer type | Results | Ref |
| *: A2AR & A2BR antagonist. RCC: renal cell cancer; mCRPC: metastatic castration resistant prostate cancer; NSCLC: non-small cell lung cancer; TNBC: triple-negative breast cancer; TIGIT: T cell immunoreceptor with Ig and ITIM domains; ORR: objective response rate; PD-1: programmed cell death protein 1; PD-L1: programmed cell death ligand 1. | |||||||
| CPI-444 (Ciforadenant) | Corvus | NCT02655822 | Ⅰ/ⅠB | Monotherapy or combined with atezolizumab (anti-PD-L1) | RCC mCRPC | ORR 3.0% (1/33)(monotherapy, RCC) ORR 11.4% (4/35)(combination, RCC) ORR 6.4% (3/47)(mCRPC) | [38, 40] |
| NCT04280328 | ⅠB | Daratumumab (anti-CD38) | Relapsed or refractory multiple myeloma | ||||
| NCT03337698 | ⅠB/Ⅱ | Atezolizumab | NSCLC | ||||
| NCT03454451 | Ⅰ/ⅠB | CPI-006 (anti-CD73) | Advanced solid tumor | ||||
| MK-3814A (Preladenant) | Merck | NCT03099161 | ⅠB/Ⅱ | Monotherapy or combine with pembrolizumab (anti-PD-1) | Advanced solid tumor | ||
| AZD4635 | AstraZeneca | NCT02740985 | Ⅰ | Monotherapy or combined with Durvalumab (anti-PD-L1)，Oleclumab (anti-CD73)，chemotherapy | Advanced solid tumor | ORR 6.1% (2/33) (monotherapy) ORR 16.2% (6/37)(combine with Durvalumab) | [46] |
| NCT04089553 | Ⅱ | Durvalumab or Oleclumab | Prostate cancer | ||||
| NCT03980821 | Ⅰ | Monotherapy | Advanced solid tumor | ||||
| NCT04495179 | Ⅱ | Durvalumab±chemotherapy | mCRPC | ||||
| NCT03381274 | ⅠB/Ⅱ | Oleclumab | NSCLC (EGFR mutation) | ||||
| TT-10 | Tarus Therapeutics | NCT04969315 | Ⅰ/Ⅱ | Monotherapy | Advanced solid tumor | ||
| AB928* (Etrumadenant) | Arcus Biosciences | NCT04892875 | ⅠB | Zimberelimab (anti-PD-1), chemoradiotherapy | Locally advanced head and neck cancers | ||
| NCT03719326 | Ⅰ/ⅠB | Chemotherapy±IPI-549 (PI3K-γ inhibitor) | TNBC, ovarian cancer | ||||
| NCT03720678 | Ⅰ/ⅠB | Chemotherapy | Gastrointestinal malignancies | ORR 9.1% (n=22) | [43] | ||
| NCT04660812 | ⅠB/Ⅱ | Zimberelimab+chemotherapy±Bevacizumab (anti-VEGF); Zimberelimab+AB680（CD73 inhibitor） | Metastatic colorectal cancer | ||||
| NCT03629756 | Ⅰ | Zimberelimab | Advanced solid tumor | ||||
| NCT04262856 | Ⅱ | Zimberelimab+ Domvanalimab (anti-TIGIT) | NSCLC (PD-L1 positive) | ||||
| NCT03846310 | Ⅰ/ⅠB | Chemotherapy, Pembrolizumab, Zimberelimab | NSCLC | ORR 42.9% (3/7) | [45] | ||
| NCT04381832 | ⅠB/Ⅱ | Zimberelimab, AB680, chemotherapy | mCRPC | ||||
| NCT05024097 | Ⅱ | Chemotherapy, radiotherapy, Zimberelimab | Rectal cancer | ||||
| NCT05177770 | Ⅱ | SRF617 (anti-CD39)+ Zimberelimab | mCRPC | ||||
| NCT04791839 | Ⅱ | Zimberelimab+Domvanalimab | NSCLC | ||||
| NCT03821246 | Ⅱ | Atezolizumab | Prostate cancer (neoadjuvant) | ||||
| NCT03193190 | ⅠB/Ⅱ | Atezolizumab+chemotherapy | Pancreatic adenocarcinoma | ||||
| NIR178/PBF-509 (Taminadenant) | Novartis | NCT03207867 | Ⅱ | PDR001 (anti-PD-1) | Advanced solid tumor; Non-Hodgkin lymphoma | ||
| NCT04237649 | Ⅰ/ⅠB | KAZ954 | Advanced solid tumor | ||||
| NCT03549000 | Ⅰ/ⅠB | NZV930 (anti-CD73)±PDR001 | Advanced solid tumor | ||||
| NCT03742349 | ⅠB | Spartalizumab (anti-PD-1)+ LAG525 (anti-LAG-3) | TNBC | ||||
| NCT04895748 | Ⅰ/ⅠB | DFF332 (Hif2α inhibitor)+ PDR001 | Renal cancer | ||||
| NCT02403193 | Ⅰ/ⅠB | Monotherapy or combined with PDR001 | NSCLC | ORR 8.3%（2/24）（monotherapy） | [42] | ||
| DZD2269 | Dizal | NCT04634344 | Ⅰ | Monotherapy | mCRPC | ||
| EOS100850 (Inupadenant) | iTeos | NCT03873883 | Ⅰ/ⅠB | Monotherapy or combine with Pembrolizumab/chemotherapy | Advanced solid tumor | ||
| NCT05117177 | Ⅰ | Monotherapy | Advanced solid tumor | ||||
| NCT05060432 | Ⅰ/Ⅱ | EOS-448 (anti-TIGIT) | Advanced solid tumor | ||||
| CS3005 | CStone | NCT04233060 | Ⅰ | Monotherapy | Advanced solid tumor | ||
| PBF-999 | Palobiofarma | NCT03786484 | Ⅰ/ⅠB | Monotherapy | Advanced solid tumor | ||
| INCB106385* | Incyte | NCT04580485 | Ⅰ | Monotherapy or combine with INCMGA00012 (anti-PD-1) | Advanced solid tumor | ||
| NCT04989387 | Ⅰ | INCA00186 (anti-CD73)±Retifanlimab (anti-PD-1) | Advanced solid tumor | ||||