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.
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).
