INFORM2 Niv Ent

Pediatric patients aged 2-21 years with refractory/relapsed/progressive high-risk malignancies with a high mutational load (group A), with high PD-L1 mRNA expression (group B), with MYC(N) amplification (group C) and with a low mutational load, low PD-L1 mRNA expression and no MYC(N) amplification (Biomarker low group D) are eligible for this trial. In addition, relapsed solid tumors and brain tumors with tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) can be included (Group E). Extensive molecular profiling (e.g. INFORM Registry) is mandatory before inclusion into the trial. T cell infiltration (TIL/TLS) is automatically determined by the INFORM Registry, but can also be done using an IHC-based screen. Patients receive a combination therapy with entinostat and nivolumab.

Nivolumab is an immune-checkpoint inhibitor and is already approved in Europe for adults. Entinostat is a novel class I selective HDACi. Clinical trials investigating the combination of nivolumab and entinostat in children have not been reported so far.

In this study the safety and activity of the combination treatment with entinostat and nivolumab for the age groups 2-11 and 12-21 years is evaluated. It can also be administered as a suspension.