INFORM2-NivEnt in detail

INFORM2-NivEnt is an exploratory multinational phase I/II combination study of nivolumab and entinostat in children and adolescents with refractory high-risk malignancies.

The title of the study is:

„INFORM2 exploratory multinational phase I/II combination study of Nivolumab and Entinostat in children and adolescents with refractory high-risk malignancies".

Inclusion of patients in Germany is possible since 26.07.2019.

Pediatric patients aged 6-21 years with refractory/relapsed/progressive high-risk malignancies with 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. Extensive molecular profiling (e.g. INFORM Registry) is mandatory before inclusion into the trial. Patients receive combination therapy with entinostat and nivolumab.

Nivolumab is an immune- checkpoint inhibitor and is already approved for adults in Europe. 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 6-11 and 12-21 years is evaluated.

Objectives

Phase I

  • To determine the recommended phase II dose (RP2D) of the combination treatment with nivolumab and entinostat administered to adolescents 12-21 years
  • To determine the recommended phase II dose (RP2D) of the combination treatment with nivolumab and entinostat administered to children 6-11 years

Phase II

  • To evaluate activity and safety of the combination treatment of nivolumab and entinostat in children and adolescents with refractory/relapsed/progressive high-risk solid tumors and CNS tumors in four different groups:
    Group A: a high mutational load (> 100 somatic SNVs/exome)
    Group B: PD-L1 high mRNA expression (RPKM > 3)
    Group C: Focal MYC(N) amplification or
    Group D: Patients with biomarker low tumors according to the definitions of group A-C.

Key inclusion criteria

  • Children and adolescents with refractory/relapsed/progressive high-risk malignancies
  • No standard of care treatment available
  • Age at registration ≥ 6 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 ≤ 12 weeks
  • Disease that is measurable as defined by RANO criteria or RECIST v1.1

Key exclusion criteria

  • Patients with CNS tumors or metastases who are neurologically unstable despite adequate treatment
  • Major surgery within 21 days of the first dose
  • Previous allogeneic bone marrow, stem cell or organ transplantation
  • Any anticancer therapy within 4 weeks or at least 5 halflives of study drug administration.

Sponsor and Financing

The Sponsor of the trial is the Heidelberg University Hospital

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 German Cancer Aid (#70112951 ENABLE)
  • Drug support by Bristol-Myers Squibb and Syndax

International monitoring is conducted by ECRIN

Participating sites

Germany:

Charité Berlin, Essen University Hospital, Hannover Medical School, Heidelberg University Hospital, Regensburg University Hospital

Europe:

Prinses Maxima Center Netherlands, Karolinska Institute Sweden, Curie Institute France

Australia:

Sydney Children’s Hospital, Royal Children’s Hospital, Melbourne and Perth Children’s Hospital

Further information

The inclusion and exclusion criteria and further information about the INFORM2-NivEnt study can be found here (ClinicalTrials.gov, NCT03838042).

EudraCT-number: 2018-000127-14 (see EU clinical trial register).

An information brochure for patients and families in German can be downloaded here.

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