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

Overview

TRX518-001 is an open label, non-randomized single group assignment, Phase 1 single dose escalation study in adults with biopsy proven unresectable Stage III or Stage IV melanoma or other solid tumor malignancies. Part A: The study objectives are to determine the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of TRX518 and to define the maximum tolerated dose at which there are tolerable side effects and/or maximum PK/PD parameter changes. Subjects will be assigned to a cohort in the order screening is completed. Dose will depend upon the cohort in which a subject is enrolled and cohorts will be dosed consecutively by ascending dose. Part A has been completed. Part B: A Dose-Escalation Study of Multi-dose TRX518 Monotherapy with objectives including characterization of the safety, tolerability, and pharmacokinetics, as well as, evaluate for evidence of anti-tumor activity and assess TRX518 immunogenicity. Part C: An Expansion Cohort of Multi-dose TRX518 Monotherapy at the Maximum Tolerated Dose

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.