Immuntherapy for children and adolescents with high-risk refractory cancers - INFORM2-NivEnt

“INFORM2 exploratory multinational phase I/II combination study of nivolumab and entinostat in children and adolescents with refractory high-risk malignancies”

Pediatric patients aged 2-21 years with refractory/relapsed/progressive high-risk malignancies with a high mutational load (group A), with MYC(N) amplification or ATRT-MYC subgroup (group C) and with high Tcell infiltration or tertiary lymphoid structures (group E) are eligible for this trial. Extensive molecular profiling (e.g. INFORM Registry) is mandatory before inclusion into the trial. 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.

The inclusion of patients in Germany is possible since 26.07.2019.

Key Inclusion criteria

Children and adolescents with refractory/relapsed/progressive high-risk malignancies
No standard of care treatment available
Age at registration ≥ 2 to ≤ 21 years
Molecular analysis for biomarker identification e.g. via INFORM molecular diagnostic platform
Time between biopsy/puncture/resection of the current refractory/relapsed/progressive tumor and registration ≤ 24 weeks. In patients receiving therapy not impacting stratification, time between biopsy/puncture/resection of the current refractory/relapsed/progressive tumor and registration of ≤ 36 weeks is allowed.
Disease that is measurable as defined by RANO criteria or RECIST v1.1

Further Information

Project Management: Venukah Schäfer

Participating sites:

Germany: Charité Berlin, Essen University Hospital, Hannover Medical School, Heidelberg University Hospital, Augsburg University Hospital
Europe: Prinses Máxima Center Netherlands, Karolinska Institute Sweden, Curie Institute France, St. Anna Children’s Hospital Austria, Children’s Hospital Zurich Switzerland
Australia: Sydney Children’s Hospital, Royal Children’s Hospital, Perth Children’s Hospital, Children's Hospital at Westmead

Financing:

The trial is funded by intramural grants (Personalized Therapy Program of the National Center for Tumor Diseases Heidelberg (NCT 3.0) of the DKFZ)
Group C (patients with MYC(N) amplified tumors) is funded by the Deutsche Krebshilfe (#70112951 ENABLE)
Study medication will be supplied by Bristol-Myers Squibb and Syndax

International monitoring is conducted by ECRIN.

For more information, see the Study Registry: The study is registered with the U.S. National Institutes of Health (ClinicalTrials.gov, NCT03838042 )

EudraCT-number: 2018-000127-14.