**14.3 Combination of immune checkpoint inhibitors with MEK inhibitors**

Suppression of the MAPK signaling pathway, which is frequently unregulated in TNBC and is correlated with enhanced proliferation of cells and shows resistance towards apoptosis, is another approach for combining immune checkpoint inhibitors with targeted therapy [98]. In the phase 2 COLET (NCT02322814) trial, cobimetinib the MEK1/2 inhibitor was combined with atezolizumab and PAX/ nab-paclitaxel as a primary therapy in patients with LD or mTNBC. According to preliminary findings, paclitaxel in combination with nab-paclitaxel has a 34% ORR, while nab-paclitaxel has a 29% ORR [99]. Clinical studies of binimetinib the

**Figure 5.** *Diagram representing the targets of immune checkpoint inhibitors.*

*Integrating Immunotherapy with Chemotherapy: A New Approach to Drug Repurposing DOI: http://dx.doi.org/10.5772/intechopen.100183*


#### **Table 6.**

*Current clinical trials for cancer vaccine and immunotherapy.*

MEK inhibitor in conjunction with pembrolizumab (NCT03106415) or avelumab (NCT03971409) in patients with LD or mTNBC are also underway (**Figure 5**).
