3CI Study: Childhood Cancer Combination Immunotherapy. Phase 1b and Expansion Study of Nivolumab Combination Immunotherapy in Children, Adolescent and Young Adult (CAYA) Patients with Relapsed/Refractory Hypermutant Cancers

Primary Objective

Primary: To confirm the safety and tolerability of nivolumab-based combination therapy. Secondary: To assess objective overall response rate (ORR) to the nivolumab-based combination therapy.

Study category: Cancer

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TMB is the total amount of genetic changes or “mutations” found in tumor cells. Some studies in adults with cancer have shown that patients with a higher TMB are more likely to respond to immunotherapy drugs. Participants who have an elevated TMB may be eligible to take part in the treatment portion of this study (Part 2) and get a combination of two immunotherapy drugs.


Child to Adult


- Patients must be ≥ 12 months and ≤ 25 years of age at the time of Part 1 informed consent/assent. - Patients must have histologically or cytologically confirmed malignancy at the time of initial diagnosis, relapse, or recurrence. -Suspicion of Hypermutant Tumor: • Microsatellite instability (MSI-H). • Mutation causing functional loss of mismatch repair gene expression (MLH1, MSH2, MSH6, PMS2, EPCAM, MSH3). • Hypermutation in any tumor (including primary malignancy for patients with relapse or previous cancer diagnoses). • Functional mutation of POLE or POLD1 genes. A syndrome linked to hypermutant cancer predisposition such as congenital mismatch repair deficiency (CMMRD), Lynch syndrome, or xeroderma pigmentosum (XP) is also permitted. - A tumor tissue specimen must be provided for molecular profiling, including TMB analysis.

Type of Study



Childrens Hospital Colorado

Principal Investigator
Margaret Macy,  MD

Margaret Macy, MD

Study ID

Protocol Number: 21-2688

More information available at ClinicalTrials.gov: NCT04500548


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