Table 3.
Combinative treatments for metastatic melanoma.
| Category | Applied Treatments for Melanoma Patients | Details (Clinical Trial ID) |
References |
|---|---|---|---|
| Double combination | Trametinib (MEKi) Dabrafenib (BRAFi) |
Improvement of PFS and OS than BRAFi as alone | [46,47,48,97] |
| Nivolumab (anti PD-1 Ab) Ipilimumab (anti CTLA-4 Ab) |
Improvements of PFA and OS than ipilimumab (NCT01844505) |
[74] | |
| Triple combination | Dabrafenib (BRAFi) Trametinib (MEKi) Pembrolizumab (anti PD-1 Ab) |
BRAFV600-mutated metastatic melanoma patients (NCT02130466) |
[102] |
| Dabrafenib (BRAFi) Trametinib (MEKi) Pembrolizumab (anti PD-1 Ab) |
Phase 2, randomized double-blind placebo-control (NCT02130466) |
[73] | |
| Cobimetinib (MEKi) Vemurafenib (BRAFi) Atezolizumab (anti-PD-L1 Ab) |
Phase Ib, BRAFV600-mutated metastatic melanoma patients (NCT01656642) | [103] | |
| HDACi combination | Pembrolizumab (anti PD-1 Ab) Entinostat (HDACi) |
Progression to metastatic melanoma on eye (NCT02697630) |
[117] |
| Ipilimumab (anti CTLA-4 Ab) Panobinostat (HDACi) |
Advanced and unresectable melanoma patients (NCT02032810) |
[112] | |
| Pembrolizumab (anti PD-1 Ab) Entinostat (HDACi) |
Melanoma patients, showing significant resistances on prior PD-1 blockade or prior PD-1/CTLA-4 blockade (NCT02437136) |
[118,119] | |
| Dabrafenib (BRAFi) Trametinib (MEKi) Entinostat (HDACi) |
On treating melanoma models of harboring mutations of BRAF, NRAS, and NF1 | [120] | |
| Anti PD-1 ab (from BioXCell) LBH589 (HDACi) |
Slower tumor progression and increased survival compared with control and single treatments in B16F10 mice model | [113] | |
| Anti-PD-1 ab (from BioXCell) AR42 (HDACi) |
Enhanced immunotherapy response with HDACi in B16 mice model | [116] |