Clinical Trials /

Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma

NCT03070392

Description:

To evaluate the overall survival of HLA-A*0201 positive adult patients with previously untreated advanced UM receiving IMCgp100 compared to Investigator's Choice of dacarbazine, ipilimumab, or pembrolizumab.

Related Conditions:
  • Uveal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma
  • Official Title: A Phase II Randomized, Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Compared With Investigator Choice in HLA-A*0201 Positive Patients With Previously Untreated Advanced Uveal Melanoma

Clinical Trial IDs

  • ORG STUDY ID: IMCgp100-202
  • NCT ID: NCT03070392

Conditions

  • Uveal Melanoma

Interventions

DrugSynonymsArms
IMCgp100IMCgp100
DacarbazineDTIC-Dome, DTIC, DIC, Imidazole CarboxamideInvestigator's Choice
IpilimumabYervoyInvestigator's Choice
PembrolizumabKeytrudaInvestigator's Choice

Purpose

To evaluate the overall survival of HLA-A*0201 positive adult patients with previously untreated advanced UM receiving IMCgp100 compared to Investigator's Choice of dacarbazine, ipilimumab, or pembrolizumab.

Detailed Description

      This Phase II study is designed to evaluate the safety and efficacy of IMCgp100 compared with
      Investigator's Choice (dacarbazine, ipilimumab or pembrolizumab) in HLA-A*0201 positive adult
      patients with advanced UM treated in the first line setting with no prior systemic or
      liver-directed chemo-, radio- or immune-therapy administered in the advanced setting (prior
      surgical resection of liver metastases and adjuvant systemic therapy are acceptable).
      Comparison of the IMCgp100 efficacy results in this Phase II study will be made with the
      concurrently randomized arm (Investigator's Choice) with a primary endpoint of overall
      survival (OS) and secondary efficacy endpoints of progression-free survival (PFS), objective
      response rate (ORR), duration of response (DOR), and disease control rate (DCR).
    

Trial Arms

NameTypeDescriptionInterventions
IMCgp100ExperimentalBiologic:IMCgp100 (Soluble gp 100-specific T cell receptor with anti - CD3 scFV: IMCgp100)
    Investigator's ChoiceActive Comparator1 of 3 Investigator's Choice options: Systemic Dacarbazine 1 of 3 Investigator's Choice options: Systemic Ipilimumab 1 of 3 Investigator's Choice options: Systemic Pembrolizumab
    • Dacarbazine

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Male or female patients age ≥ 18 years of age at the time of informed consent
    
              2. Ability to provide and understand written informed consent prior to any study
                 procedures
    
              3. Histologically or cytologically confirmed metastatic UM
    
              4. No prior systemic therapy in the metastatic or advanced setting
    
              5. No prior local, liver-directed therapy; prior surgical resection of oligometastatic
                 liver disease is allowed
    
              6. Prior neoadjuvant or adjuvant therapy is allowed provided administered in the curative
                 setting in patients with localized disease
    
            Exclusion Criteria:
    
              1. Impaired baseline organ function as evaluated by out-of-range laboratory values
    
              2. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs
                 or monoclonal antibodies
    
              3. Clinically significant cardiac disease or impaired cardiac function
    
              4. Presence of symptomatic or untreated central nervous system (CNS) metastases
    
              5. Active infection requiring systemic antibiotic therapy
    
              6. Known history of human immunodeficiency virus infection (HIV)
    
              7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
    
              8. Malignant disease, other than that being treated in this study
    
              9. Patients receiving systemic steroid therapy or any other systemic immunosuppressive
                 medication. Local steroid therapies are acceptable
    
             10. History of adrenal insufficiency, pneumonitis, interstitial lung disease, or
                 inflammatory bowel disease
    
             11. Major surgery within 2 weeks of the first dose of study drug
    
             12. Radiotherapy within 2 weeks of the first dose of study drug, with the exception of
                 palliative radiotherapy to a limited field
    
             13. Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GM-CSF, M-CSF) ≤ 2
                 weeks prior to start of study drug
    
             14. Pregnant, likely to become pregnant, or lactating women
          
    Maximum Eligible Age:99 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall survival defined as the time from patient inclusion to date of death due to any cause
    Time Frame:Survival status will be assessed every 3 months from randomization until death, assessed up to 40 months.
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Safety defined as the number of patients with treatment emergent adverse events, laboratory abnormalities, ECG changes, and/or physical examination findings
    Time Frame:Safety will be assessed from informed consent through 90 days after end of treatment
    Safety Issue:
    Description:
    Measure:Efficacy: Objective response rate (ORR) defined as the proportion of patients achieving an objective response (RECIST v1.1) by Independent Central Review
    Time Frame:ORR will be assessed every 3 months from randomization until disease progression, assessed up to 40 months
    Safety Issue:
    Description:
    Measure:Efficacy: Duration of response (DOR) defined as the time from first documented objective response (RECIST v1.1) by Independent Central Review until the date of documented disease progression
    Time Frame:DOR will be assessed every 3 months from randomization until disease progression, assessed up to 40 months
    Safety Issue:
    Description:
    Measure:Efficacy: Progression free survival (PFS) defined as the time from randomization to the date of progression (RECIST v1.1) by Independent Central Review or death due to any cause
    Time Frame:PFS will be assessed every 3 months from randomization until disease progression or death, assessed up to 40 months
    Safety Issue:
    Description:
    Measure:Efficacy: Disease control rate (DCR) defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1) by Independent Central Review.
    Time Frame:DCR will be assessed every 3 months from randomization until disease progression, assessed up to 40 months
    Safety Issue:
    Description:
    Measure:Quality-of-Life: General health status will be assessed using the EQ-5D,5L questionnaire
    Time Frame:: EQ-5D,5L will be assessed every 6 weeks from randomization for 24 weeks and approximately every 3 months thereafter until death, assessed up to 40 months
    Safety Issue:
    Description:
    Measure:Quality-of-Life: Health related quality of life will be assessed using EORTC QLQ-C30 questionnaire
    Time Frame:EORTC QLQ-C30 will be assessed every 6 weeks from randomization for 24 weeks and approximately every 3 months thereafter until disease progression, assessed up to 40 months
    Safety Issue:
    Description:
    Measure:Pharmacokinetics (IMCgp100 Arm only): Area under the plasma concentration-time curve (AUC)
    Time Frame:AUC will be assessed weekly for 3 weeks and every 6 weeks thereafter until end of treatment, assessed up to 40 months
    Safety Issue:
    Description:
    Measure:Pharmacokinetics (IMCgp100 Arm only): The maximum observed plasma drug concentration after single dose administration (Cmax)
    Time Frame:Cmax will be assessed weekly for 3 weeks and every 6 weeks thereafter until end of treatment, assessed up to 40 months
    Safety Issue:
    Description:
    Measure:Pharmacokinetics (IMCgp100 Arm only): The time to reach maximum plasma concentration (Tmax)
    Time Frame:Tmax will be assessed prior to and after the first three doses of IMCgp100, an average of 3 weeks
    Safety Issue:
    Description:
    Measure:Pharmacokinetics (IMCgp100 Arm only): The elimination half-life (t1/2)
    Time Frame:t1/2 will be assessed prior to and after the first three doses of IMCgp100, an average of 3 weeks
    Safety Issue:
    Description:
    Measure:Pharmacokinetics (IMCgp100 Arm only): To assess the frequency of anti-IMCgp100 antibody formation
    Time Frame:Approximately 5 assessments will be performed between first dose of IMCgp100 and end of treatment, assessed up to 40 months
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Immunocore Ltd

    Trial Keywords

    • Melanoma
    • Uveal Cancer
    • IMCgp100
    • Immunotherapy

    Last Updated

    October 11, 2017