Study of Nivolumab and Ipilimumab in Children and Young Adults With INI1-Negative Cancers

Inclusion Criteria

• •All participants must have one of the following histologically confirmed tumors at original diagnosis or relapse:
• •* Stratum 1
• •* Malignant rhabdoid tumor (MRT)
• •* Rhabdoid tumor of the kidney (RTK)
• •* Epithelioid sarcoma
• •* Chordoma (poorly differentiated or de-differentiated)
• •* Other INI1-negative or SMARCA4-deficient malignant tumors (with PI approval)
• •* Stratum 2
• •* Atypical teratoid rhabdoid tumor (ATRT)
• •* Other INI1-negative or SMARCA4-deficient primary CNS malignant tumors (with PI approval)
• •All participants must have tumor assessment at original diagnosis or relapse showing the following:
• •* Loss of INI1 confirmed by immunohistochemistry (IHC), OR
• •* Molecular confirmation of tumor bi-allelic SMARCB1 (INI1) loss or mutation when INI1 IHC is equivocal or unavailable
• •* Loss of SMARCA4 confirmed by IHC or molecular confirmation of tumor bi-allelic SMARCA4 loss or mutation when SMARCA4 is equivocal or unavailable
• •Relapsed or refractory disease and no standard treatment options as determined by locally or regionally available standards of care and treating physician's discretion
• •Measurable disease as defined by RECIST v1.1 (Stratum 1) or RANO criteria (Stratum 2)
• •Karnofsky performance status ≥ 50% for participants ≥16 years of age and Lansky performance status ≥ 50% for participants \<16 years of age
• •Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy. Participants must meet the following minimum washout periods prior to first day of study treatment:
• •* Myelosuppressive chemotherapy: At least 14 days after the last dose of myelosuppressive chemotherapy
• •* Radiotherapy
• •* At least 14 days after local palliative XRT (small port)
• •* At least 90 days must have elapsed after prior TBI, craniospinal XRT or if \>50% radiation of pelvis
• •* At least 42 days must have elapsed if other substantial BM radiation
• •* At least 42 days must have passed since last radionuclide therapy (e.g. samarium or radium)
• •* Small molecule biologic therapy: At least 7 days following the last dose of a nonmonoclonal biologic agent
• •* Monoclonal antibody: At least 21 days after the last dose
• •* Myeloid growth factors: At least 14 days following the last dose of long-acting growth factor (e.g. Neulasta) or 7 days following short-acting growth factor
• •* Stem Cell or Autologous T Cell Infusion: At least 42 days must have elapsed after stem cell or autologous T cell infusion
• •Participants must have adequate organ function as defined below
• •* Bone Marrow Function
• •* Absolute neutrophil count ≥500/uL
• •* Platelets ≥50,000/uL and transfusion independent
• •* Hepatic Function
• •* Total bilirubin ≤ 1.5 x upper limit of normal for age
• •* ALT (SGPT) ≤ 3 x upper limit of normal
• •* Renal function
• •* A serum creatinine within protocol limits based on age/sex. OR
• •* Creatinine clearance ≥ 70 mL/min/1.73 m2 for participants with creatinine levels above institutional normal
• •* Adequate Pulmonary Function Defined as: no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficient and a pulse oximetry \> 92% while breathing room air
• •* Adequate pancreatic function defined as serum lipase ≤ ULN at baseline
• •* Negative B-HCG pregnancy test in females of childbearing potential (must be drawn within 24 hours prior to initial administration of nivolumab)
• •* Women of childbearing potential (WOCBP) receiving nivolumab agree to adhere to contraception for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and who are sexually active with WOCBP will agree to adhere to contraception for a period of 7 months after the last dose of nivolumab.
• •* Ability to understand and/or the willingness of the patient (or parent or legally authorized representative, if minor) to provide informed consent using an institutionally approved informed consent procedure.