COM-IT-2 Background/study objectives

First line combination of immunotherapy and chemotherapy gives objective response rates of 50-60%, but unfortunately most patients progress within the first year of treatment. For patients with oligo-metastatic disease, definitive radiotherapy has shown improved survival. Non-ablative radiation-doses have been found to increase the response of immunotherapy by an increased release of neoantigens triggering immunogenic cell death. Exhausted CD8+ and CD4+ T-cells have been found associated with reduced effect of immunotherapy, and various regulatory cells and expression of check-point proteins are associated with treatment failure. There is limited knowledge of mechanisms of resistance in immunoradiotherapy and strategies to stratify treatment based on biomarkers. Evidence of toxicity of extensive radiotherapy with immunotherapy is limited. 

The primary objective of the trial is to identify biomarkers of response/resistance to propose the optimal combination of immunotherapy and radiotherapy for patients with stage IV NSCLC. The immune response in responders will be compared to non-responders for characterisation of the extracellular matrix and circulating cytokines and immune cells. At time of progression, we will have blood samples and a few biopsies. Toxicity and efficacy of the treatment will be evaluated. Translational and clinical data will be combined to design a definitive study of immunotherapy and radiotherapy for patients with stage IV NSCLC, possibly with treatment strategy based on biomarkers at baseline aiming at increased survival.