Clinical Trial Finder

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).

The following visits are required: Part A:

• - Screening visit: 1 to 2 appointments will be conducted to determine eligibility.

All or most requirements can be determined from the patient's medical records.

• - Baseline visit: within 7 days of the planned study dosing day a baseline physical exam, blood tests and electrocardiogram will be obtained.

• - Dosing visit: 1 outpatient visit where TRX518 will be given IV over 1 hour followed by 4 hours of observation and some repeat blood tests.

• - Follow up visits: 5 outpatient visits following dosing at 1, 8 and 15 days and 3, 6, 12, and 18 weeks post dosing - Long term follow-up: 4 brief assessments by medical record review and/or telephone contact at 6, 12, 18, and 24 months post dosing.

• - The core study duration is 18 weeks.

The follow-up study duration is 24 months. Parts B & C:

• - Screening/Baseline visit: 1 appointment will be conducted to perform testing and evaluations for eligibility within 28 days of the first dosing day.

• - Dosing Visits: Each subject will receive IV doses of TRX518 once every other week (e.g., D1 and D15) in 28-day cycles - Follow up visits: When a patient stops treatment, they will enter the Follow-up Period and have an End of Treatment study visit approximately 30 days after the last dose of study drug.

Subsequently, patients will have long-term follow-up approximately every 12 weeks until death or lost to follow up.