SRS and Nivolumab in Treating Patients With Newly Diagnosed Melanoma Metastases in the Brain or Spine

PRIMARY OBJECTIVES:

I. To assess the safety profile of stereotactic radiosurgery with nivolumab in combination to
treat patients with newly diagnosed melanoma brain or spinal metastases.

SECONDARY OBJECTIVES:

I. To estimate local control rate in brain and spine. II. To estimate systematic control
rate. III. To estimate progression-free survival.

TERTIARY OBJECTIVES:

I. To explore peripheral blood immune response during and after treatment.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 60 minutes on day 1. Patients then undergo
stereotactic radiosurgery on day 8 per standard of care. Courses with nivolumab repeats every
14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 10 weeks, and
then every 3 months thereafter.

Inclusion Criteria:

- Patients must have histologically confirmed diagnosis of melanoma; the pathologic
confirmation may be from another metastatic site or from metastatic brain or spine
lesions

- Patients must have stage IV melanoma, with newly identified brain or spine metastases

- Patients must have measurable lesion in the brain or spine that is >= 3 mm seen on
magnetic resonance imaging (MRI) with contrast; NOTE: contrasted pre-treatment MRI
scan must be obtained =< 21 days prior to stereotactic radiosurgery treatment

- Karnofsky performance scale >= 70%

- Leukocytes >= 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 glutamate pyruvate transaminase [SGPT]) =< 2.5 x
institutional upper limit of normal

- Creatinine within normal institutional limits OR according to Johns Hopkins MRI policy

- Women of child bearing potential (WOCBP) must use a reliable form of contraception
during the study treatment period and for up to 12 weeks following the last dose of
study drug

- Men must agree to the use of male contraception during the study treatment period and
for at least 12 weeks after the last dose of study drug

- Ability to understand and the willingness to sign written informed consent document(s)

Exclusion Criteria:

- Prior whole brain radiation or conventional radiation to the spine at the site of new
lesion

- Prior chemotherapy within 28 days of starting treatment

- Prior therapy with investigational drugs within 28 days or at least 5 half-lives
(whichever is longer) before study administration

- Prior therapy with an anti- programmed cell death 1 (PD-1), anti- programmed cell
death-ligand 1 (PD-L1), or anti-PDL-2 antibody

- Neurologic dysfunction that would confound the evaluation of neurologic and other
adverse events

- Known allergy to compounds of similar chemical or biologic composition to nivolumab

- Pregnant or breastfeeding women

- Known history of human immunodeficiency virus

- Active infection requiring therapy, 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; exceptions include those
with vitiligo or resolved childhood asthma/atopy; subjects with asthma who require
intermittent use of bronchodilators (such as albuterol) will not be excluded from this
study

- Use of any vaccines against infectious diseases (e.g. varicella, influenza, etc.) up
to 4 weeks (28 days) before receiving nivolumab

- Prisoners or subjects who are compulsorily detained for treatment of either a
psychiatric or physical (e.g. infectious disease) illness

- Patients with both brain and spine metastases will be excluded from the trial

- Patients who are allergic to MRI contrast agent or have contraindication for MRI