Neoadjuvant Nivolumab plus Ipilimumab for the Treatment of Malignant and Pre-Malignant Peripheral Nerve Sheath Tumors

Inclusion Criteria

• Patients must have histologically confirmed diagnosis of ANNUBP, low grade MPNST or high grade MPNST in accordance with the diagnostic criteria of Miettinen MM et al, Human Pathology 2017 via biopsy
• Patients may have plexiform neurofibroma or other tumors such as optic pathway glioma, other low-grade glioma or other neoplasm in addition to the ANNUBP, low grade MPNST or high grade MPNST that is stable (has not required treatment in the last 12 months and is not anticipated to need treatment in the next 12 months)
• Measureable disease by RECIST criteria in at least one site
• Karnofsky Performance Scale ≥ 60%
• No contraindications for nivolumab or ipilimumab
• White blood cells (WBC) ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤ 2 X institutional upper limit of normal
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 X institutional upper limit of normal
• Creatinine within normal institutional limits OR according to institutional magnetic resonance imaging (MRI) policy
• Women of child bearing potential (WOCBP) must use an adequate method to avoid pregnancy for 5 months plus the time required for Nivolumab to undergo approximately five half-lives after the last dose of investigational drug. In order for a woman to be determined not of child-bearing potential, she must have ≥ 12 months of non-therapy-induced amenorrhea or be surgically sterile
• Men receiving nivolumab or ipilimumab 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 investigational product
• Ability to understand and the willingness to sign written informed consent document(s)

Exclusion Criteria

• Chemotherapy or other investigational agent for the current episode of newly diagnosed atypical neurofibroma or MPNST
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL-2 antibodies
• Known allergy to compounds of similar chemical or biologic composition to nivolumab or ipilimumab
• Pregnant or breastfeeding women
• Known history of human immunodeficiency virus
• Active infection requiring therapy, including known positive tests for hepatitis B surface antigen or hepatitis C ribonucleic acid (RNA)
• Active autoimmune disease, history of autoimmune disease or history of syndrome that required systemic steroids or immunosuppressive medications, e.g. organ, tissue, or allogenic hematopoietic stem cell transplant (HSCT) recipients. Exceptions include those with resolved childhood asthma/atopy. Subjects with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study. Subjects are also permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Patients are excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Use of any vaccines against infectious diseases (e.g. varicella, influenza, etc.) up to 4 weeks (28 days) before receiving nivolumab and ipilipumab
• Prisoners or subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness
• Prior radiation doses equivalent to, or greater than, 8000 cGy to the target lesions at 200 cGy fractions at any timepoint
• Any radiation to the the target lesions within 6 months of enrollment
• Other concurrent severe and/or uncontrolled medical disease, which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal [GI] tract ulceration, congestive heart failure, etc.)