Table 2.
Combinational treatment strategies for CM.
| Biological Classification |
Drug Name | Mechanism | Main Target | Study |
|---|---|---|---|---|
| Combined Targeted Therapy | ||||
| Kinase Inhibitor | Dabrafenib + Trametinib | inhibition of BRAF-MEK pathway reactivation, decreased tumor cell survival in BRAF-mutants | BRAF mutant, MEK |
NCT01584648 NCT0159790 |
| Vermurafenib + Cobimetinib | NCT01689519 | |||
| Encorafenib + Binimetinib | COMBO450 | |||
| ICI + Combined Targeted Therapy | ||||
| Monoclonal Antibody + Kinase Inhibitor | Pembrolizumab + Dabrafenib + Trametinib | PD1 checkpoint blockade, decreased tumor cell survival in BRAF-mutants | PD1, RAF, MEK | NCT02130466 |
| Atezolizumab + Vermurafenib + Cobimetinib | PDL1 checkpoint blockade, decreased tumor cell survival in BRAF-mutants | PDL1, RAF, MEK |
NCT02908672 IMspire150 |
|
| Intratumoral Stimulation | ||||
| Cytokine | GM-CSF | stimulation of tumor immune response by GM-CSF | APCs, TILs | E4697 |
| IL-2 | stimulation of tumor immune response by IL2 | TILs, NK cells |
NCT01672450 NCT00204581 |
|
| Oncolytic Virus | Talimogene laherparepvec (T-VEC) | oncolysis, activation of anti-tumor immune response through IFN signalling | tumor cells, innate and adaptive Immunity | NCT00769704 |
| ONCOS-102 | oncolysis, immune activation by GM-CSF | tumor cells, innate and adaptive Immunity | NCT03003676 | |
| Plasmid | Tavokinogene telseplasmid | stimulating diffentiation, activation of the adaptive immune system | APCs, TILs | NCT01502293 |
| TLR9 agonists | SD-101; IMO-2125; CMP-001; CPG 7909 | induction of CD8 T cell response enhancing uptake, destruction of cancer cells | TLR9 in APCs, TILs |
NCT02521870 NCT02644967 NCT02680184 |
| STING agonists | ADU-S100, MK-1454 | anti-tumor response through type I IFN signalling activation | STING in tumor cells, TIL, APCs |
NCT02675439 NCT03172936 NCT03010176 |
| Immune Checkpoint Inhibition + Intratumoral Stimulation | ||||
| Oncolytic Virus + Monoclonal Antibody | T-VEC + Ipilimumab | immunological priming of TME to enhance PD-1 blockade efficacy | tumor cells, TILs, APCs | NCT01740297 |
| T-VEC + Pembrolizumab | MASTERKEY265 KEYNOTE034 |
|||
| ONCOS-102 + Pembrolizumab | NCT03003676 | |||
| Intratumoral Stimulation + Targeted Therapy | ||||
| Oncolytic Virus + Kinase Inhibitor | T-VEC + Trametinib | oncolysis, adaptive immune activation, MEK inhibition to reduce tumor cell survival | tumor cells, MEK, TILs and APCs | NCT03088176 |
| ICI + Anti-Angiogenesis | ||||
| Monoclonal Antibody | Bevacizumab | vessel normalization, immunomodulation, checkpoint inhibition | VEGF | AVAST-M |
| Ipilimumab + Bevacizumab | CTLA4, VEGF | NCT01950390 | ||
| Atezolizumab + Bevacizumab | PDL1, VEGF | NCT04091217 | ||
| Monoclonal Antibody + Neutralizing Peptibody | Pembrolizumab + AMG386 | vessel normalization, immunomodulation, checkpoint inhibition | PD1, Angpt1/2 | NCT03239145 |
| Tremelimumab + MEDI3617 | CTLA4, Angpt2 | NCT02141542 | ||