Galectin Inhibitor (GR-MD-02) and Ipilimumab in Patients With Metastatic Melanoma

This study will employ a 3+3 phase I design with dose escalation of GR-MD-02 in conjunction
with the standard therapeutic dose of ipilimumab in patients with advanced melanoma for whom
ipilimumab would be considered standard of care. In addition to monitoring for toxicity and
clinical response, blood samples will be obtained to assess immunologic measures relevant to
galectin biology and ipilimumab T-cell check-point inhibition

Inclusion Criteria:

- Patients with metastatic or unresectable melanoma for whom treatment with ipilimumab
is indicated. Histological confirmation of melanoma will be required by previous
biopsy or cytology.

- Patients must be ≥ 18 years of age.

- Eastern Collaborative Oncology Group (ECOG) performance status of 0-1.

- Women of childbearing potential must have a serum or urine pregnancy test performed
within 72 hours prior to the start of protocol treatment. The results of this test
must be negative in order for the patient to be eligible. In addition, women of
childbearing potential as well as male patients must agree to take appropriate
precautions to avoid pregnancy.

- No active bleeding.

- Anticipated lifespan greater than 12 weeks.

- Patients must sign a study-specific consent document.

Exclusion Criteria:

- Patients who have previously received a galectin antagonist

- Prior ipilimumab to treat metastatic melanoma (prior ipilimumab in the adjuvant
setting is permitted if the patient did not experience ≥ grade 3 toxicity related to
immunotherapy.

- Patients with active autoimmune disease except for autoimmune thyroiditis or vitiligo.

- Patients with history of colitis

- Patients with untreated brain metastases. Patients with treated brain metastases who
demonstrate control of brain metastases with follow-up imaging 4 or more weeks after
initial therapy are eligible.

- Other active metastatic cancer requiring treatment.

- Patients with active infection requiring antibiotics.

- Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo
or fetus.

- Laboratory exclusions (to be performed within 28 days of enrollment):

- Need for chronic steroids. Inhaled corticosteroids are acceptable.

- Inability to give informed consent and comply with the protocol. Patients with a
history of psychiatric illness must be judged able to understand fully the
investigational nature of the study and the risks associated with the therapy.

- Any medical condition that in the opinion of the Principal Investigator would
compromise the safety or conduct of the study procedures.