Nivolumab or Nivolumab and Azacitidine in Patients With Recurrent, Resectable Osteosarcoma

Treatment will be administered in 28 day cycles with the first cycle in the neoadjuvant
setting. This will be followed by surgery to render the participant in surgical remission.
Subsequently the participant will continue to receive treatment for up to 12 additional
cycles or until recurrence, whichever occurs first. For participants with known bilateral
lung recurrence, the nodule[s] in one lung should be resected, prior to the first cycle of
chemotherapy.

Inclusion Criteria:

- Participants must have had a histologic diagnosis of osteosarcoma at original
diagnosis

- Disease Status: Patients with an isolated pulmonary recurrence of osteosarcoma can be
enrolled on this study.

- Any history of metastatic disease at a site other than lung would make the
patient ineligible for this study.

- The patient's treating team must consider the patient's disease to be resectable
and the patient must be willing to undergo resection of all disease, including
any lung lesion meeting criteria for likely metastatic disease, defined as: 3 or
more lesions ≥ 3 mm in diameter OR a single lesion ≥ 5 mm.

- Patients with bilateral disease are eligible provided their disease is considered
resectable. Resectable pulmonary nodules are defined as nodules that can be
removed without performing a pneumonectomy (e.g., nodules immediately adjacent to
the main stem bronchus or main pulmonary vessels).

- Must have a performance status corresponding to Eastern Cooperative Oncology Group
(ECOG) scores of 0, 1 or 2, using the Karnofsky scale for patients > 16 years of age
and the Lansky scale for patients ≤ 16 years of age

- Prior Therapy: Participants must have fully recovered from the acute toxic effects of
all prior chemotherapy, immunotherapy, or radiotherapy prior to the start of protocol
therapy.

- Participants must have normal organ and marrow function within 7 days of starting
protocol therapy

- All participants and/or their parents or legal guardians must have the ability to
understand and the willingness to sign a written informed consent/assent document

- Additional criteria may apply

Exclusion Criteria:

- Pregnancy or Breast Feeding

- Males and females of reproductive potential may not participate unless they have
agreed to the use of, at minimum, two methods of contraception, with one method being
highly effective and the other method being either highly effective or less effective
as outlined in study protocol documentation

- Concomitant Medications: Patients receiving the following are not eligible:

- Corticosteroids or other immunosuppressive medications

- Patients who are currently receiving other investigational agents or other anti-cancer
therapy

- Intercurrent Illnesses: Patients with uncontrolled intercurrent illness including, but
not limited to:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness/social situations that would limit compliance with study
requirements

- Autoimmune disorders: Patients with a history of any Grade autoimmune disorder are not
eligible.

- Asymptomatic laboratory abnormalities (e.g., ANA, rheumatoid factor, altered thyroid
function studies) will not render a patient ineligible in the absence of a diagnosis
of an autoimmune disorder.

- Patients with ≥ Grade 2 hypothyroidism due to history of autoimmunity are not
eligible. Note: Hypothyroidism due to previous irradiation or thyroidectomy will not
impact eligibility

- Allergies: Patients with a history of allergic reactions attributed to compounds of
similar chemical or biologic composition to Nivolumab (e.g., another humanized
antibody) or Azacitidine are not eligible

- Safety and Monitoring: Patients who are considered unable to comply with the safety
monitoring requirements of the study are not eligible

- Patients with known HIV or hepatitis B or C are excluded

- Patients who have received prior solid organ transplantation are not eligible

- Patients who have received prior anti-PD-1 directed therapy (mAb or small molecule)
are not eligible