Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03070392
Recruitment Status : Recruiting
First Posted : March 3, 2017
Last Update Posted : October 1, 2019
Sponsor:
Information provided by (Responsible Party):
Immunocore Ltd

Tracking Information
First Submitted Date  ICMJE February 14, 2017
First Posted Date  ICMJE March 3, 2017
Last Update Posted Date October 1, 2019
Actual Study Start Date  ICMJE October 16, 2017
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
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. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03070392 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma
Official Title  ICMJE 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
Brief Summary 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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Uveal Melanoma
Intervention  ICMJE
  • Biological: IMCgp100
    IMCgp100 is to be administered at 20 mcg cycle 1 day1, then 30 mcg cycle 1 day 8, then 68 mcg cycle 1 day 15 and weekly thereafter by IV infusion over 15 minutes until confirmed disease progression or unacceptable toxicity
  • Drug: Dacarbazine
    Dacarbazine is to be administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity
    Other Names:
    • DTIC-Dome
    • DTIC
    • DIC
    • Imidazole Carboxamide
  • Biological: Ipilimumab
    Ipilimumab is to be administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments
    Other Name: Yervoy
  • Biological: Pembrolizumab
    Pembrolizumab is to be administered at 2 mg/kg IV infusion over 30 minutes every 3 weeks until confirmed disease progression or unacceptable toxicity
    Other Name: Keytruda
Study Arms  ICMJE
  • Experimental: IMCgp100
    Biologic:IMCgp100 (Soluble gp 100-specific T cell receptor with anti - CD3 scFV: IMCgp100)
    Intervention: Biological: IMCgp100
  • Active Comparator: Investigator's Choice

    1 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

    Interventions:
    • Drug: Dacarbazine
    • Biological: Ipilimumab
    • Biological: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 28, 2017)
327
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Shaad Abdullah, MD 484-534-5261 clinicaltrials@immunocore.com
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Germany,   Italy,   Netherlands,   Poland,   Spain,   Switzerland,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03070392
Other Study ID Numbers  ICMJE IMCgp100-202
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Immunocore Ltd
Study Sponsor  ICMJE Immunocore Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Immunocore Ltd
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP