Clinical Trials /

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

NCT01239134

Description:

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

Related Conditions:
  • Malignant Solid Tumor
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Trial of TRX518 (Anti-GITR mAb) in Stage III or IV Malignant Melanoma or Other Solid Tumors
  • Official Title: Part A: A First-in-Human Single Ascending Dose Study of TRX518 in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma or Other Solid Tumor Malignancies Part B: A Dose-Escalation Study of Multi-dose TRX518 Monotherapy Part C: An Expansion Cohort of Multi-dose TRX518 Monotherapy at the Maximum Tolerated Dose

Clinical Trial IDs

  • ORG STUDY ID: TRX518-001
  • NCT ID: NCT01239134

Conditions

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

Interventions

DrugSynonymsArms
TRX518TRX518

Purpose

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

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
TRX518Experimental
  • TRX518

Eligibility Criteria

        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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: Adverse Events
Time Frame:through 30 days post last dose
Safety Issue:
Description:Any adverse change in health or side effect from the initiation of the study drug dose through completion or premature withdrawal

Secondary Outcome Measures

Measure:Part A: Evaluate the effect of TRX518 on lymphoid cell subset number and function
Time Frame:At baseline and at various timepoints up to 6 weeks post dose
Safety Issue:
Description:
Measure:Part A: Assess TRX518 immunogenicity
Time Frame:At baseline and at various timepoints up to 18 weeks post dose
Safety Issue:
Description:
Measure:Part A: Evaluate the effect of TRX518 on long-term safety measuring vital signs, tumor status, adverse events
Time Frame:At Months 6, 12, 18 and 24
Safety Issue:
Description:
Measure:Parts B & C: TRX518 peak concentration (Cmax)
Time Frame:At each study visit from baseline up to end of treatment visit
Safety Issue:
Description: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
Measure:Parts B & C: Time to peak concentration (Tmax)
Time Frame:At each study visit from baseline up to end of treatment visit
Safety Issue:
Description: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
Measure:Parts B & C: Area under the curve (AUC)
Time Frame:At each study visit from baseline up to end of treatment visit
Safety Issue:
Description: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
Measure:Parts B & C: Evaluate multi-dose TRX18 monotherapy for any evidence of antitumor activity (objective response rate, [ORR] progression free survival [PFS], duration of response and overall survival [OS]; RECIST v1.1 will be utilized
Time Frame:Every 8 weeks while on study treatment and every 12 weeks for survival until death or lost to follow up.
Safety Issue:
Description:objective response rate [ORR], progression free survival [PFS], duration of response [DoR] and overall survival [OS]); RECIST v1.1 criteria will be utilized
Measure:Parts B & C: Evaluate the effect of multi-dose TRX518 monotherapy on lymphoid cell subset number and function
Time Frame:At baseline and at various timepoints up to end of treatment visit
Safety Issue:
Description:
Measure:Parts B & C: Assess TRX518 immunogenicity
Time Frame:At baseline and at various timepoints up to end of treatment visit
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Leap Therapeutics, Inc.

Trial Keywords

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

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