Immunotherapy (Nivolumab and Ipilimumab) for the Treatment of Relapsed or Refractory INI-1 Negative Cancer

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 principal investigator [PI] approval) * Stratum 2 ** Atypical teratoid rhabdoid tumor (ATRT) ** Other INI1-negative or SMARCA4-deficient primary central nervous system (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; OR, * 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 version (v)1.1 for Stratum 1; OR, * RANO for Stratum 2 ** Note: RECIST v 1.1 may be used for disease evaluation for in Stratum 2 (CNS-primary tumor) patients whose only measurable disease is extra-cranial in location
• Age >= 6 months and =< 40 years
• 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 radiation therapy (XRT) (small port) ** At least 90 days must have elapsed after prior total body irradiation (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
• Absolute neutrophil count >= 500/uL
• Platelets >= 50,000/uL and transfusion independent, defined as not receiving a platelet transfusion for at least 7 days prior to CBC documenting eligibility
• Total bilirubin =< 1.5 x upper limit of normal for age
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x upper limit of normal (for the purpose of this study, the upper limit of normal [ULN] for ALT is 45 U/L)
• A serum creatinine based on age/gender as follows OR creatinine clearance >= 70 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal * Age: Maximum Serum Creatinine (mg/dL) * 6 months to 1 year: 0.5 (male and female) * 1 to < 2 years: 0.6 (male and female) * 2 to < 6 years: 0.8 (male and female) * 6 to < 10 years: 1 (male and female) * 10 to < 13 years: 1.2 (male and female) * 13 to < 16 years: 1.5 (male), 1.4 (female) * >= 16 years: 1.7 (male), 1.4 (female)
• No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficient and a pulse oximetry > 92% while breathing room air
• Serum lipase =< ULN at baseline
• Negative beta-human chorionic gonadotropin (B-HCG) pregnancy test (urine or serum) in females of childbearing potential. Must be drawn or repeated 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, documented using an institutionally approved informed consent procedure

Exclusion Criteria

• Participants who are receiving any other investigational agents
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. CNS subjects receiving corticosteroids for neurologic symptom relief must be at stable or decreasing doses for at least 7 days prior to the first day of study treatment. For all patients, corticosteroid doses of up to 0.12 mg/kg/day prednisone equivalent may be approved after consultation with the Principal Investigator. Treatment with topical, inhaled or ophthalmic corticosteroid is acceptable
• Participants with a known history of human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis C (testing not required as part of screening)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or any other concurrent disease which in the judgment of the Investigator would make the subject inappropriate for enrollment on this study
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are exceptions. Intermittent use of bronchodilators or local steroid injections are not excluded. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diagnoses not listed must be approved by the principal investigator
• Patients who have received prior solid organ transplantation are not eligible
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Women of childbearing potential (WOCBP) receiving nivolumab will be instructed 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 be instructed to adhere to contraception for a period of 7 months after the last dose of nivolumab
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. OX-40, CD137)
• Participants who have received live / attenuated vaccine within 30 days of first dose of study treatment