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.
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
378
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
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
Ipilimumab is to be administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments
Efficacy: Overall Survival
Overall survival is defined as the time from randomization to date of death due to any cause.
Time frame: From randomization to the data cut off date of 13-Oct-2020; median follow-up duration was 14.1 months.
Safety: Number of Participants With Treatment Emergent Adverse Events
Safety was defined as the number of participants with treatment emergent adverse events, including laboratory abnormalities, ECG changes, and/or physical examination findings.
Time frame: Safety was assessed from informed consent through 90 days after end of treatment, up to 36 months.
Efficacy: Progression Free Survival (PFS)
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.
Time frame: PFS was assessed every 3 months from randomization until disease progression or death, up to 36 months.
Quality-of-Life: Change From Baseline in EQ-5D,5L Domain Scores
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.
Time frame: 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.
Quality-of-life: Change From Baseline in EQ-5D Visual Analogue Score (VAS)
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.
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Pembrolizumab is to be administered at 2 mg/kg IV infusion up to a maximum of 200 mg administered Intravenously over 30 minutes every 3 weeks or 200 mg fixed dose administered intravenously every 3 weeks where approved locally until confirmed disease progression or unacceptable toxicity
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
...and 47 more locations
Time frame: 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.
Quality-of-Life: Change From Baseline in EORTC QLQ-C30 Global Health Status
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.
Time frame: 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.
Pharmacokinetics (PK): Tebentafusp Concentration
Serum PK concentrations of tebentafusp were collected over time.
Time frame: 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.
Efficacy: Objective Response Rate (ORR)
Objective response rate (ORR) is defined as the proportion of patients achieving an objective response (RECIST v1.1).
Time frame: ORR will be assessed after every participant has had at least 3 assessments, conducted every 3 months, up to 5.5 years.
Efficacy: Duration of Response (DOR)
Duration of response (DOR) is defined as the time from first documented objective response (RECIST v1.1) until the date of documented disease progression.
Time frame: DOR will be assessed every 3 months from randomization until disease progression, assessed up to 5.5 years.
Efficacy: Disease Control Rate (DCR)
Disease control rate (DCR) is defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1)
Time frame: DCR will be assessed every 3 months from randomization until disease progression, up to 5.5 years.
Pharmacokinetics: 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 5.5 years.