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RecruitingLast updated: 24 February 2026

INFORM2 NivEnt: This study aims to analyse the effectiveness of combined treatment in children and adolescents with certain high risk refractory, relapsed or progressive cancerINFORM2 Exploratory Multinational Phase I/II Combination Study of Nivolumab and Entinostat in Children and Adolescents With Refractory High-risk Malignancies

Trial purpose

Medical clipboardCancer treatment

Tumor type

Multi-Cancer Multi-Cancer

Age

People6 - 21

Trial acronym

INFORM2 NivEnt

Clinical summary

Summary

You may be eligible for this study if you are aged 2-21 years old, and have been diagnosed with a relapsed or refractory high-risk cancer or high grade glioma with a repair defect of the genetic materials.

Study details
If you are eligible to participate, you will always receive the drugs nivolumab and entinostat in combination. There will be no placebo or control group with any other medication.

Screening

Before treatment starts, there will be a screening phase. Molecular profiling (DNA sequencing of the tumour) will be performed and the molecular results will indicate if you are eligible for this study. You will be allocated to one of three biomarker groups and continue with screening. Routine tests will also be performed to confirm whether you are eligible for this study, and if you can start treatment. These include medical history, physical exam, CT or MRI scans of the tumour, ECG, blood tests and urine tests.

During treatment

Entinostat is a tablet or liquid taken once a week. Nivolumab is given at the hospital every 2 weeks, as an intravenous IV drip over 30 minutes. Routine tests will be performed during treatment to monitor your health. These include medical history, physical exam, CT or MRI scans of the tumour, ECG, blood tests and urine tests. Additional blood samples are collected for this study to measure the levels of drugs and examine how they are working in the body.

You will be in this study for up to 4 years. This includes the screening phase, study treatment (12 cycles for about 1 year), follow-up visits (every 4 weeks up to 100 days) and long term observation (every 3 months until the study closes).

Eligible cancers

Eligible cancers for this study include:

  • CNS tumours: medulloblastoma, ependymoma, ATRT, ETMR, paediatric high grade glioma (including DIPG) or other paediatric embryonal CNS tumours, OR
  • Solid tumours: neuroblastoma, nephroblastoma, rhabdoid tumour, embryonal or alveolar rhabdomyosarcoma or other embryonal small round blue cell tumours including paediatric type (bone) sarcoma, OR
  •  Children and adolescents with newly diagnosed high grade glioma (HGG) in the context of a constitutional mismatch repair deficiency syndrome after maximum safe surgical resection with no established standard of care treatment option with curative intention available

Conditions

This trial is treating patients with refractory, relapsed or progressive cancer

Eligibility

Inclusion

- Children and adolescents with refractory/relapsed/progressive high-risk
-- CNS tumours: medulloblastoma, ependymoma, ATRT, ETMR, paediatric high grade glioma (including DIPG) or other paediatric embryonal CNS tumours OR
-- solid tumours: neuroblastoma, nephroblastoma, rhabdoid tumour, embryonal or alveolar rhabdomyosarcoma or other embryonal small round blue cell tumours including paediatric type (bone) sarcoma OR
-- Children and adolescents with newly diagnosed high grade glioma (HGG) in the context of a constitutional mismatch repair deficiency syndrome after maximum safe surgical resection with no established standard of care treatment option with curative intention available
- No standard of care treatment available
- Age at registration greater than or equal to 2 years to less than or equal to 21 years
- Molecular analysis for biomarker identification (SNV load, high TILs or TLS positive, MYC/N amplification) in laboratories complying with DIN EN ISO/IEC 17025 or similar via INFORM molecular diagnostic platform or equivalently valid molecular pipeline
- Biomarker determined using whole exome sequencing (SNV load), IHC (high TILs or TLS positive) and whole genome sequencing (MYC/N amplification)
- In case molecular analysis was not performed via INFORM molecular pipeline: transfer of molecular data (whole genome sequencing)
- Time between biopsy/puncture/resection of the current refractory/relapsed/progressive tumour and registration less than or equal to 24 weeks
- Disease that is measurable as defined by RANO criteria or RECIST v1.1.
- Life expectancy > 3 months, sufficient general condition score (Lansky greater than or equal to 70 or Karnofsky greater than or equal to 70). Transient states like infections requiring antibiotic treatments can be accepted, and also stable disabilities resulting from disease/surgery (hemiparesis, amputations etc.) can be accepted and will not be considered for Lansky/Karnofsky assessments.
- Laboratory requirements:
-- Hematology: absolute granulocytes greater than or equal to 1.0 × 10^9/L (unsupported), platelets greater than or equal to 100 × 10^9/L, hemoglobin greater than or equal to 8 g/dL or greater than or equal to 4.96 nmol/L
-- Biochemistry: Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN) AST(SGOT) less than or equal to 3.0 x ULN, ALT(SGPT) less than or equal to 3.0 x ULN, serum creatinine less than or equal to 1.5 x ULN for age
- ECG: normal QTc interval according to Bazett formula < 440ms
- Patient is able to swallow oral study medication
- Ability of patient and/or legal representative(s) to understand the character and individual consequences of clinical trial
- Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment. Sexually active women of childbearing potential must agree to use acceptable and appropriate contraception during the study and for at least 6 months after the last study treatment administration. Sexually active male patients must agree to use a condom during the study and for at least 7 months after the last study treatment administration.
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- Before patient screening and registration, written informed consent, also concerning data and blood transfer, must be given according to ICH/GCP, and national/local regulations.
- No prior therapy with the combination of immune checkpoint inhibitors and HDACi
- Phase I: molecular analysis performed and biomarker status known (mutational load, high TILs or TLS positive and MYC(N) amplification status).
- Phase II: molecular analysis performed, biomarker status known (mutational load, high TILs or TLS positive and MYC(N) amplification status) and stratification according to the following criteria:
-- Group A: High mutational load (defined as > 100 somatic SNVs/exome) based on whole exome sequencing or
-- Group C: Focal MYC(N) amplification based on whole genome sequencing or ATRT-MYC subgroup or
-- Group E: High TILs or TLS positive (defined as cells per mm^2 > 600 or presence of tertiary lymphoid structure) based on IHC analysis

Exclusion

- Patients with CNS tumours or metastases who are neurologically unstable despite adequate treatment (e.g. convulsions).
- Patients with low-grade gliomas or tumours of unknown malignant potential are not eligible
- Evidence of > Grade 1 recent CNS haemorrhage on the baseline MRI scan.
- Participants with bulky CNS tumour on imaging are ineligible; bulky tumour is defined as:
-- Tumour with any evidence of uncal herniation or severe midline shift
-- Tumour with diameter of > 6 cm in one dimension on contrast-enhanced MRI
-- Tumour that in the opinion of the investigator, shows significant mass effect
- Previous allogeneic bone marrow, stem cell or organ transplantation
- Diagnosis of immunodeficiency
- Diagnosis of prior or active autoimmune disease
- Evidence of interstitial lung disease
- Any contraindication to oral agents or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the investigator, would preclude adequate absorption.
- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). Known active hepatitis B (e.g., hepatitis B surface antigen-reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [qualitative]). Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible. HBV DNA test must be performed in these patients prior to study treatment. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Clinically significant, uncontrolled heart disease.
- Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumour biopsy and insertion of central venous access devices are not considered major surgery, but for these procedures, a 48 hour interval must be maintained before the first dose of the investigational drug is administered.
- Any anticancer therapy (e.g., chemotherapy, HDACi (including valproic acid), DNA methyltransferase inhibitors, other immunotherapy, targeted therapy, biological response modifiers, endocrine anticancer therapy or radiotherapy) within 4 weeks or at least 5 half-lives (whichever is longer) of study drug administration.
- Radiologically confirmed radiotherapy induced pseudoprogression in CNS tumours
- Traditional herbal medicines; these therapies are not fully studied and their use may result in unanticipated drug-drug interactions that may cause or confound the assessment of toxicity. As part of the enrolment/informed consent procedures, the patient will be counselled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
- History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form (including benzamide) of the investigational medicinal product.
- Participation in other ongoing clinical trials.
- Pregnant or lactating females.
- Presence of underlying medical condition (e.g. gastrointestinal disorders or electrolyte disturbances) that in the opinion of the Investigator or Sponsor could adversely affect the ability of the subject to comply with or tolerate study procedures and/or study therapy, or confound the ability to interpret the tolerability of combined administration of entinostat and nivolumab in treated subjects.
- Patients receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (up to 5mg/m^2/day prednisone equivalent) may be approved after consultation with the Sponsor.
No patient will be allowed to enrol in this trial more than once.

Inclusion

  • You have had treatment, but your cancer has come back (relapsed or recurrent).
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You have the type of cancer, symptoms, or health risks that this clinical trial is focused on.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

Recruiting hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ANZCTR, ClinicalTrials.gov, EU Clinical Trials Register *. View further details about this trial on the registry via the links below:

Trial sponsor

Minderoo Foundation, Australian and New Zealand Children's Haematology/Oncology Group

Scientific Title

INFORM2 Exploratory Multinational Phase I/II Combination Study of Nivolumab and Entinostat in Children and Adolescents With Refractory High-risk Malignancies

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