Trial of TRX518 (Anti-GITR mAb) in Stage III or IV Malignant Melanoma or Other Solid Tumors

Inclusion Criteria (Parts B \& C):

* 18 years or older
* Histologically confirmed unresectable Stage III or Stage IV malignant melanoma, or other solid tumor malignancies
* Failed to respond to or relapsed following standard treatment, declined or was not eligible for standard treatment.
* Expected survival of at least 12 weeks.
* Eastern Cooperative Oncology Group performance status score of 0 or 1 is required.
* Evidence of adequate organ function by standard laboratory tests.

Exclusion Criteria (Parts B \& C):

* Evidence of progression of central nervous system (CNS) metastases or symptomatic CNS metastases within 35 days prior to dosing.
* Ocular melanoma which has not metastasized or presence of a non-solid tumor.
* A history of any major surgery within 4 weeks prior to dosing.
* Any history of antitumor therapy completed within 28 days prior to dosing.
* Subjects with active autoimmune disease or history of known or suspected autoimmune disease, with the exception of subjects with isolated vitiligo, resolved childhood asthma/atopy, psoriasis not requiring systemic treatment and controlled thyroid disorders.
* Clinically significant heart disease, defined as NYHA Class III or IV.
* Any significant systemic infection requiring IV antibiotics.
* Known to be human immunodeficiency virus (HIV) positive, have hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCAb) unless HCV RNA undetected/negative.
* Treatment with any other anti-human GITR monoclonal antibody (mAb) or immunomodulatory therapy 42 days prior to dosing (30 days for Interleukin-2 \& Interferon-α, 7 days for Topical Imiquimod).
* Adverse events from prior anti-cancer therapy that have not resolved to grade ≤1 except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy.
* Use of any investigational drugs within 30 days prior to dosing.
* Any condition that requires or is likely to require treatment with pharmacologic doses of systemic corticosteroids. Subjects are permitted to receive physiologic replacement of corticosteroid therapy (≤ 10 mg prednisone daily).