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)
  • 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
  • Ipilimumab
  • Pembrolizumab

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

November 11, 2019