Table 3.
The most promising and innovative approaches to overcome such resistance
| Targeted molecule | therapeutic combination | Results | Trial |
|---|---|---|---|
| IDO | Epacadostat (IDO1 enzyme inhibitor) + Pembrolizumab | 40% objective response (62 total patient) | ECHO-202/KEYNOTE 037 |
| Epacadostat + Pembrolizumab or Placebo | Failed to improve OS or PFS | ECHO-301/KEYNITE-252 | |
| CSF1R | CSF1R inhibitors + ICI | Ongoing | NCT02718911/NCT02526017 |
| STING | Inhibitor + Pembrolizumab | Ongoing | NCT03010176 |
| RIG-1 | Inhibitor + Pembrolizumab | Ongoing | NCT03739138 |
| TIM3 | No clinical trials focusing on mccRCC | ||
| LAG3 | Anti-LAG-3 antibody + ICI | Ongoing | NCT02996110 |
| Relatlimab (Anti-LAG-3) + Nivolumab | Ongoing | NCT02996110 | |
| LAG3 and CTLA4 | XmAb22841 (bispecific) + Pembrolizumab or alone | Ongoing | NCT03849469 |
IDO: indoleamine 2,3-dioxygenase; CSF1R: colony stimulating factor 1 receptor; STING: stimulator of IFN genes; RIG-1: retinoic acid-inducible gene 1; TIM3: 1-5 T cell immunoglobulin mucin-3; LAG3: lymphocyte-activation gene 3; CTLA4: cytotoxic T-lymphocyte antigen-4; ICI: immune checkpoint inhibitors; PFS: progression free survival; OS: overall survival; mccRCC: metastatic clear cell renal cell carcinoma