Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma
- Conditions
- Uveal Melanoma
- Interventions
- Registration Number
- NCT03070392
- Lead Sponsor
- Immunocore Ltd
- 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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 378
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Investigator's Choice Pembrolizumab 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 Investigator's Choice Ipilimumab 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 IMCgp100 (tebentafusp, Kimmtrak) IMCgp100 Biologic:IMCgp100 (Soluble gp 100-specific T cell receptor with anti - CD3 scFV: IMCgp100) Investigator's Choice Dacarbazine 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
- Primary Outcome Measures
Name Time Method Efficacy: Overall Survival From randomization to the data cut off date of 13-Oct-2020; median follow-up duration was 14.1 months. Overall survival is defined as the time from randomization to date of death due to any cause.
- Secondary Outcome Measures
Name Time Method Safety: Number of Participants With Treatment Emergent Adverse Events Safety was assessed from informed consent through 90 days after end of treatment, up to 36 months. Safety was defined as the number of participants with treatment emergent adverse events, including laboratory abnormalities, ECG changes, and/or physical examination findings.
Quality-of-Life: Change From Baseline in EORTC QLQ-C30 Global Health Status EORTC QLQ-C30 was assessed at baseline (Cycle 1 Day 1) and on Day 1 of every other cycle to Cycle 5 Day 1, every fourth cycle thereafter, beginning with Cycle 9 Day 1 and End of Treatment (EOT), up to 36 months. Each cycle is 21 days. Global health status and quality of life was assessed using the EORTC QLQ-C30 questionnaire. The score range for the EORTC QLQ-C30 is from 0 to 100, with higher scores indicating better functioning and better global health status and health-related quality of life. A positive change indicates improvement.
Efficacy: Duration of Response (DOR) DOR will be assessed every 3 months from randomization until disease progression, assessed up to 5.5 years. Duration of response (DOR) is defined as the time from first documented objective response (RECIST v1.1) until the date of documented disease progression.
Pharmacokinetics: Frequency of Anti-IMCgp100 Antibody Formation Approximately 5 assessments will be performed between first dose of IMCgp100 and end of treatment, assessed up to 5.5 years. Efficacy: Progression Free Survival (PFS) PFS was assessed every 3 months from randomization until disease progression or death, up to 36 months. Progression free survival (PFS) is defined as the time from randomization to the date of progression (RECIST v1.1) or death due to any cause.
Efficacy: Objective Response Rate (ORR) ORR will be assessed after every participant has had at least 3 assessments, conducted every 3 months, up to 5.5 years. Objective response rate (ORR) is defined as the proportion of patients achieving an objective response (RECIST v1.1).
Efficacy: Disease Control Rate (DCR) DCR will be assessed every 3 months from randomization until disease progression, up to 5.5 years. Disease control rate (DCR) is defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1)
Quality-of-life: Change From Baseline in EQ-5D Visual Analogue Score (VAS) EQ-5D,5L VAS was assessed at baseline (Cycle 1 Day 1) and on Day 1 of every other cycle to Cycle 5 Day 1, every fourth cycle thereafter, beginning with Cycle 9 Day 1 and End of Treatment (EOT), up to 36 months. Each cycle is 21 days. The EQ-5D VAS score records the participant's self-rated health on a vertical visual analogue scale, with 0 being the worst imaginable health state and 100 being the best imaginable health state. A positive change indicates improvement.
Pharmacokinetics (PK): Tebentafusp Concentration PK concentrations were assessed at pre-dose, end of infusion and anytime in the 12 to 24 hour window after completion of the infusion in Cycle 1 on Days 1, 8 and 15. Serum PK concentrations of tebentafusp were collected over time.
Quality-of-Life: Change From Baseline in EQ-5D,5L Domain Scores EQ-5D,5L was assessed at baseline (Cycle 1 Day 1) and on Day 1 of every other cycle to Cycle 5 Day 1, every fourth cycle thereafter, beginning with Cycle 9 Day 1 and End of Treatment (EOT), up to 36 months. Each cycle is 21 days. General health status was assessed using the EQ-5D,5L questionnaire, which includes five dimensions (5D): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 scoring levels, where 1 indicates a better health state (no problems) and 3 indicates a worse health state. A positive change indicates improvement.
Trial Locations
- Locations (57)
UCLA Medical Center
🇺🇸Los Angeles, California, United States
The Angeles Clinic and Research Institute
🇺🇸Los Angeles, California, United States
Byers Eye Institute, Stanford University
🇺🇸Palo Alto, California, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
University of Miami - Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
The University of Chicago Medicine
🇺🇸Chicago, Illinois, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
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