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

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.

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).