Avadomide (CC-122) in Combination With Nivolumab in Advanced Melanoma

Inclusion Criteria:

- Unresectable or metastatic melanoma of cutaneous, mucosal, conjunctival, or unknown
origin. Uveal melanoma is not permitted. Cohort 1: Naïve to anti-PD1 therapy Cohort 2:
Progressed on previous anti-PD1 therapy. Subjects who have received anti-PD1 therapy
in the adjuvant setting for previously resected melanoma are eligible for this cohort
provided they have not received any intervening systemic therapy for the relapse

- Be willing and able to provide written informed consent for the trial.

- Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)
version 1.1

- Females of childbearing potential should have a negative urine or serum pregnancy test
within 72 hours prior to receiving the first dose of study medication.

- Females of childbearing potential should be willing to use 2 methods of birth control
or be surgically sterile, or abstain from heterosexual activity for the course of the
study through 180 days after last dose of study medication.

- Males should agree to use an adequate method of contraception starting with the first
dose of study therapy through 180 days after the last dose of study therapy.

- Adequate organ function

Exclusion Criteria:

- Has received an investigational drug or other anti-cancer therapy within 3 weeks of
the first dose of treatment or < 5 half-lives of that agent, whichever is shorter. Any
toxicity from prior therapy must have recovered to < grade 1.

- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment (only exception to this is the need for steroids for CNS metastases; see #6
below). Inhaled, intra-articular, or topical steroids are permissible.

- Has a history of hypersensitivity to nivolumab.

- Has a known additional malignancy that is progressing or requires active treatment,
the lack of which would pose a risk to the health of the subject, in the opinion of
the investigator.

- Has known symptomatic central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate provided
they are stable without evidence of progression by imaging for at least four weeks
after definitive intervention and using no more than the equivalent of dexamethasone
2mg/d for the management of vasogenic edema, if necessary. This exception does not
include carcinomatous meningitis, which is excluded regardless of clinical stability.

- Active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy [ insufficiency, etc.) is not considered a form of systemic treatment. Patients with
previous grade III/IV toxicity from immunotherapy that led to treatment
discontinuation are excluded.

- Has an active infection requiring systemic therapy.

- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial, in the opinion of the investigator.

- Is pregnant or breastfeeding.

- Has a known history of Human Immunodeficiency Virus (HIV), active Hepatitis B or
Hepatitis C.

- Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed