Nivolumab and Ipilimumab in Treating Patients With Metastatic Uveal Melanoma

PRIMARY OBJECTIVES:

I. Overall response rate.

SECONDARY OBJECTIVES:

I. Progression-free survival. II. Median overall survival. III. One-year overall survival.

EXPLORATORY OBJECTIVES:

I. Tissue and blood correlates to define immune infiltration and signatures as a result of
treatment with nivolumab plus ipilimumab.

OUTLINE:

INDUCTION PHASE: Patients receive nivolumab intravenously (IV) over 60 minutes and ipilimumab
IV over 90 minutes during weeks 1, 4, 7, and 10. Treatment continues for 12 weeks in the
absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Patients not experiencing disease progression or unacceptable toxicity by
week 12 of the induction phase receive nivolumab IV every 2 weeks. Treatment continues in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 60 days.

Inclusion Criteria:

- Willing and able to give written informed consent

- History of uveal melanoma and documented metastatic disease with at least one
measurable lesion is required; which is >= 1 cm x 1 cm (on spiral computed tomography
[CT] or equivalent)

- Any number of prior therapies is allowed

- White blood cell (WBC) >= 2000/uL

- Absolute neutrophil count (ANC) >= 1500/uL

- Platelets >= 100 x 10^3/uL

- Hemoglobin >= 9 g/dL

- Creatinine =< 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) > 40
mL/min (using the Cockcroft-Gault formula)

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN for
patients without liver metastasis, =< 5 x ULN for liver metastases

- Bilirubin =< 1.5 x ULN, (except patients with Gilbert's syndrome, who must have a
total bilirubin less than 3.0 mg/dL)

- In suspected patients no active or chronic infection with human immunodeficiency virus
(HIV), hepatitis B, or hepatitis C

- Performance status Eastern Cooperative Oncology Group (ECOG) 0-1

- Baseline imaging in the form of CT chest, abdomen, pelvis with oral and intravenous
contrast within 28 days of study entry; for patients with a contrast allergy, choice
of alternative body imaging will be at the discretion of the investigator or his
designee; magnetic resonance imaging (MRI) of the brain is only needed if clinically
indicated

- Prior to start of treatment must be more than 21 days elapsed from surgery, radiation
therapy, or prior chemotherapy; more than 42 days elapsed from prior immune therapy
including vaccines

- Women of childbearing potential (WOCBP) and fertile men with partners of childbearing
potential must be using an adequate method of contraception to avoid pregnancy
throughout the study and for up to 26 weeks after the last dose of investigational
product, in such a manner that the risk of pregnancy is minimized

Exclusion Criteria:

- Untreated primary uveal melanoma except in cases where metastatic disease is diagnosed
at the time of primary disease

- Metastatic uveal melanoma patients with bone-only disease

- Any other malignancy from which the patient has been disease-free for less than 2
years, with the exception of adequately treated and cured basal or squamous cell skin
cancer, superficial bladder cancer or carcinoma in situ of the cervix, breast, or
prostate

- Autoimmune disease: Patients with a history of inflammatory bowel disease, including
ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients
with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic
progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
vasculitis [e.g., Wegener's Granulomatosis]; motor neuropathy considered of autoimmune
origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis)

- Any underlying medical or psychiatric condition, which in the opinion of the
investigator will make the administration of ipilimumab hazardous or obscure the
interpretation of adverse events (AEs), such as a condition associated with frequent
diarrhea

- Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to
1 month before or after any dose of ipilimumab)

- Concomitant therapy with any of the following: tamoxifen, toremifene, IL 2,
interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy;
immunosuppressive agents; other investigation therapies; or chronic use of systemic
corticosteroids greater than physiologic replacement doses; ocular steroid use is
acceptable; (a) concomitant palliative radiation for the purposes of symptom
management is allowed

- Women of childbearing potential (WOCBP) who: (a) are unwilling or unable to use an
acceptable method of contraception to avoid pregnancy for their entire study period
and for up to 26 weeks after cessation of study drug, or (b) have a positive pregnancy
test at baseline, or (c) are pregnant or breastfeeding

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