Table 2.
Results from clinical trials combining immune checkpoint inhibitors with inhibitors of the PI3K/AKT/mTOR pathway or MAPK pathway in melanoma and TNBC.
| Identifier | Phase | Combination | Drug Names | Indications | Results |
|---|---|---|---|---|---|
|
NCT03742102 (BEGONIA) |
Ib/II | AKTi + αPDL1 + Chemo | Capivasertib Durvalumab Paclitaxel |
Metastatic PD-L1+ TNBC | ORR = 16/30 (53.3%) G3/4 trAE =22/30 (73%) |
| NCT03961698 (Mario-3) | II | PI3Kγi + α-PDL1 + Chemo | Eganelisib Atezolizumab Nab-paclitaxel |
Locally advanced unresectable or metastatic TNBC |
ORR = 21/38 (55.3%) |
| NCT02908672 (IMspire150) | III | B-RAFi + MEK1/2i → B-RAFi + MEK1/2i + α-PDL1 |
Vemurafenib Cobimetinib Atezolizumab |
Advanced unresectable BRAFV600E melanoma | PFS = 15.1mo vs. 10.6mo G3/4 trAE = 79% vs. 73% n = 514 |
| NCT02130466 (KEYNOTE-22) | I/II | B-RAFi +MEK1/2i + α-PD1 | Dabrafenib Trametinib Pembrolizumab |
Unresectable or metastatic BRAFV600E melanoma | PFS = 16.9mo vs. 10.7mo G3-5 trAE = 58% vs. 25% n =120 |
|
NCT02967692 (COMBI-i) |
III | B-RAFi + MEK1/2i + α-PD1 | Dabrafenib Trametinib Spartalizumab |
Unresectable or metastatic BRAFV600E melanoma | PFS = 16.2mo vs. 12.0mo G3-5 trAE = 55% vs. 33% n = 532 |
|
NCT02224781 (DREAMSeq) |
III | α-PD1 + α-CTLA4 (IT) or BRAFi + MEK1/2i (TT) first, switch treatment upon progression | Nivolumab-Ipilimumab Dabrafenib-trametinib |
Metastatic BRAFV600E melanoma | 2-yr OS = 72% vs. 52% n = 265 |
|
NCT02631447 (SECOMBIT) |
II | B-RAFi MEK1/2i (TT) or α-PDL1 + α-CTLA4 (IT) first, switch treatment upon progression, or TT(8wks) + IT until progression + TT | Nivolumab-Ipilimumab Encorafenib-Binimetinib |
Metastatic BRAFV600E melanoma | 2-yr OS = 62% vs. 73% vs. 69% 3-yr OS = 53% vs. 63% vs. 60% G3/4 trAE = 28% vs. 54% vs. 32% n = 251 |
ORR, objective response rate. trAE, treatment-related adverse events. OS, overall survival. PFS, progression-free survival.