SARC038: Phase 2 Study of Regorafenib and Nivolumab in Osteosarcoma

Inclusion Criteria: * Age ≥ 5 years at the time of enrollment. Every effort will be made to ensure that 50% of patients will be ≤ 21 years of age. * Histologically confirmed high grade osteosarcoma (excluding osteosarcoma associated with Paget disease of bone or extraskeletal osteosarcoma) at diagnosis or relapse. Must have relapsed or refractory osteosarcoma following at least one line of systemic therapy for the initial treatment of osteosarcoma. * Performance Status: Lansky (≤ 16 years of age) or Karnofsky (\>16 years of age) performance score of ≥ 70, or Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1. See Appendix A. Patients who are unable to walk because of paralysis, but who are up and about in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * At least one site of measurable disease on CT/MRI scan as defined by RECIST 1.1. Baseline imaging must be performed within 21 days of Day 1 of study therapy. * Must be able to swallow intact pills * Adequate organ and bone marrow function within 7 days of Day 1 of study therapy defined as: * Absolute Neutrophil Count (ANC) ≥ 1000/mm3 * Platelets ≥ 75 000/mm3 * Hemoglobin ≥ 8 g/ dL (transfusions allowed) * ALT and AST ≤ 3 x institutional upper limit of normal (ULN) or ≤ 5.0 x institutional ULN if considered due to tumor * Serum albumin ≥ 3 g/dL * Serum total bilirubin ≤ 1.5 x institutional ULN. NOTE: Patients with elevated bilirubin secondary to Gilbert's disea…