The Joint Funding project TRUST is the translational research project of the ongoing multicenter phase I clinical study IT-PD1/NOA-26. The study explores the safety and efficacy of a PD1 antibody in metastatic solid tumors with leptomeningeal disease (LMD, meningeosis neoplastica). Enrolled patients are treated with intrathecal applications of PD1 antibody Nivolimab and monitored by longitudinal collection of biosamples (cerebrospinal fluid, blood and tissue) and MR imaging. In the present study, we aim at further understanding the LMD-associated tumor microenvironment during intrathecal immune checkpoint inhibition. Therefore, we will perform an in-depth investigation of cellular, molecular and metabolic features of longitudinal biosamples from enrolled patients.

The successful introduction of immune checkpoint inhibitors such as PD1 antibodies led to a significant expansion of therapeutical options for solid as well as hematologic cancers. By their indirect activation of the immune system, cancer cells can be damaged by tumor-specific T-lymphocytes. For patients with LMD, a highly aggressive subform of metastatic disease of the central nervous system (CNS), intravenously administered PD1 antibody therapy already showed clinical efficacy. By intrathecal application, we now aim for increased efficacy and reduced systemic side effects. The overall objective of the study is therefore, to improve the drug tolerance and the median overall survival time of LMD patient by Nivolumab therapy.