A Phase II Trial of Avelumab in Patients With Recurrent or Progressive Osteosarcoma

Inclusion Criteria

• Patients must be > 12 years of age but 16 years of age and the Lansky scale for patients ≤ 16 years of age.
• Patients must have a life expectancy of ≥ 6 weeks.
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• Myelosuppressive chemotherapy: must not have received within 3 weeks of entry onto this study.
• Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent.
• Immunotherapies: at least 42 days must have elapsed since a prior therapy that included a monoclonal antibody or any other type of immunotherapy (e.g. chimeric antigen receptor (CAR) T cell therapy).
• Radiation therapy (RT): ≥ 2 weeks for local palliative RT (small port); ≥ 6 months must have elapsed if prior craniospinal RT or if ≥ 50% radiation of the pelvis; ≥ 6 weeks must have elapsed if other substantial bone marrow (BM) radiation.
• Organ Function Requirements:
• Adequate bone marrow function defined as:
• Peripheral absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3 (transfusion independent)
• Hemoglobin ≥ 9.0 g/dL (may receive RBC transfusions)
• Adequate renal function defined as:
• Creatinine clearance or radioisotope GFR ≥70 mL/min/1.73m2 OR
• Serum creatinine based on age/gender as follows: (threshold creatinine values were derived from the Schwartz formula for estimating GFR).
• Age is: 12 to 2 g/dL
• Serum lipase ≤ upper limit of normal (IULN).
• Patients must have documented pulse oximetry ≥ 92% on room air.
• Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days of enrollment.
• Male or female patients who are sexually active and of reproductive potential must agree to use an effective contraceptive method throughout the study and for at least 60 days after last avelumab treatment administration. Abstinence is an acceptable form of contraception.
• Patients must not currently be using other investigational agents.
• Patients must not currently be using other anti-cancer agent.
• Patients must be able to comply with the safety monitoring of the study in the opinion of the investigator.
• Written, informed consent and assent following Institutional Review Board, NCI, FDA and OHRP guidelines.

Exclusion Criteria

• Central nervous system (CNS) metastases.
• Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
• Active infection requiring systemic therapy.
• Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
• Patient who has received vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke ( 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable
• Other severe acute or chronic medical cond