A single-arm study of the treatment of high-risk tumors with nivolumab and entinostat in children and adolescents

A high-risk tumor is a type of cancer with a particularly poor prognosis. This means that the tumor is difficult to treat, often does not respond well to standard therapies, or carries a high risk of recurrence. These tumors may have a high mutation burden, meaning that many genetic alterations are present. Some tumors exhibit amplification of the myc gene. This gene plays a crucial role in cell growth and metabolic processes, and when it is overactivated, it can promote uncontrolled cell growth. Other types of cancer exhibit high PD-L1 expression on the surface of cancer cells. The PD-L1 protein plays a role in suppressing the immune response by helping to deactivate T cells (part of the immune system). High mutation burden, MYC amplification, and PD-L1 expression are potential characteristics of high-risk tumors being investigated in this study.

Depending on the type of cancer, treatment typically involves a combination of surgery, chemotherapy, and radiation therapy. However, these approaches are not always successful. When that is the case, targeted drugs and immunotherapies show great promise. Nivolumab is a so-called immune checkpoint inhibitor that helps the immune system recognize and fight cancer cells by inactivating the PD-L1 protein on the cancer cells. It is already approved for many types of cancer, but not yet specifically for high-risk tumors in children. Entinostat is a so-called histone deacetylase inhibitor (HDACi) that influences gene regulation in cancer cells and can thus inhibit their growth. So far, it has only been used in clinical trials, where it has shown promising results, particularly in combination with nivolumab.

The INFORM2 study is a single-arm study divided into two phases. In Phase I, the optimal dosage of the combination therapy will be determined for two age groups (6–11 years and 12–21 years). Phase II will investigate the efficacy of the therapy and, for this purpose, will divide the study participants into three groups based on genetic alterations in the tumor:

Group A: Patients with a high mutation burden

Group B: Patients with MYC amplification

Group C: Patients with high PD-L1 expression

Group D: Patients with none of the genetic characteristics listed in Groups A–C

All study participants will receive the same treatment consisting of 12 cycles, with each cycle lasting 28 days and beginning with a one-week preparation phase. During the study and for up to 48 weeks after the study begins, efficacy will be assessed based on the response rate and disease progression.

To participate in the study, children and adolescents must be between 2 and 21 years of age and have a treatment-resistant or recurrent high-risk tumor with the characteristics listed above. The conditions being studied primarily include CNS tumors (brain cancer), such as gliomas and solid tumors. Patients must not have any other tumors and should be in stable general health.