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

NCT01239134 | Completed Phase 1

• 1 other identifier: TRX518-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Unresectable Stage III or Stage IV Malignant Melanoma or Other Solid Tumor Malignancies

Keywords

Malignant melanoma; Metastatic; Unresectable; Stage III or Stage IV; Solid tumor

Outcome Measures

Primary Outcomes (6)

• Part A: Adverse Events

  Any adverse change in health or side effect from the initiation of the study drug dose through completion or premature withdrawal

  through 30 days post last dose

• Part A: TRX518 peak concentration (Cmax)

  Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518

  various timepoints through 1 week post dose

• Part A: Time to peak concentration (Tmax)

  Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518

  various timepoints through 1 week post dose

• Part A: Area under the curve (AUC)

  Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518

  various timepoints through 1 week post dose

• Part A: Define a maximum single dose at which there are tolerable side effects and/or maximum PK/PcD parameter changes

  End of Cycle 1 (Day 28)

• Parts B and C: Adverse Events

  Any adverse change in health or side effect from the initiation of the study drug dose through completion or premature withdrawal

  through 30 days post dose

Secondary Outcomes (9)

• Part A: Evaluate the effect of TRX518 on lymphoid cell subset number and function

  At baseline and at various timepoints up to 6 weeks post dose

• Part A: Assess TRX518 immunogenicity

  At baseline and at various timepoints up to 18 weeks post dose

• Part A: Evaluate the effect of TRX518 on long-term safety measuring vital signs, tumor status, adverse events

  At Months 6, 12, 18 and 24

• Parts B & C: TRX518 peak concentration (Cmax)

  At each study visit from baseline up to end of treatment visit

• Parts B & C: Time to peak concentration (Tmax)

  At each study visit from baseline up to end of treatment visit

Study Arms (1)

TRX518

EXPERIMENTAL

Biological: TRX518

Interventions

TRX518 BIOLOGICAL

Humanized, Fc disabled, anti-human GITR (glucocorticoid-induced tumor necrosis factor receptor) monoclonal antibody

TRX518

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Leap Therapeutics, Inc.: lead
• Cancer Research Institute, New York City: collaborator

Study Sites (1)

Immunotherapeutics Core / Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Melanoma Trials at MSKCC

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Cynthia Sirard

  Leap Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2010
• First Posted: November 11, 2010
• Study Start: October 1, 2010
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)