Among other things, cancers are caused by a malfunction of the immune system. Therefore, targeting the immune response is a promising approach to treat tumor diseases. So-called immune checkpoint inhibitors, for example PD-L1 blocking antibodies, offer an option for this. They generate an efficient systemic immune response against tumors and, despite systemic application, are effective against many different types of solid cancer. Further research will be conducted to explore the potential for combining ICI with therapies that specifically target cancer cells. In the underlying CRAFT study (Continuous ReAssessment with Flexible exTension trial), five different agents are being combined with PD-L1 blockade. The aim is to improve the efficacy of cancer immunotherapy and to overcome treatment resistance. As part of the associated MIMETIC project (MIMETIC = Monitoring the immune modulating effects of combinatorial targeted and immune checkpoint inhibitor treatment), comprehensive monitoring of the immune status of the study participants is taking place. Both genetic and immunological factors in the tumor as well as in the periphery will be monitored, which will allow to draw conclusions about the effects of the various therapy options. By combining the complementary clinical, scientific and methodological expertise of the three DKTK partner sites in Dresden, Heidelberg and Frankfurt/Mainz, tumor and blood cells will be evaluated to characterize cancer and immune cells phenotypically and functionally. The use of state-of-the-art scientific methods such as plasmaproteomics, multiparameter flow cytometry, multispectral imaging and T-cell receptor sequencing will help to obtain a comprehensive understanding of the immunomodulatory properties of combined targeted immunotherapy.