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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03070392
Recruitment Status : Active, not recruiting
First Posted : March 3, 2017
Results First Posted : September 14, 2021
Last Update Posted : March 21, 2022
Sponsor:
Information provided by (Responsible Party):
Immunocore Ltd

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Uveal Melanoma
Interventions Biological: IMCgp100
Drug: Dacarbazine
Biological: Ipilimumab
Biological: Pembrolizumab
Enrollment 378
Recruitment Details A total of 378 patients were randomly assigned (2:1) to Tebentafusp (n=252) or Investigator's Choice (n=126) at 58 sites in 14 countries.
Pre-assignment Details The data cut-off date for this analysis was 13 October 2020. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design.
Arm/Group Title Tebentafusp Investigator's Choice: Dacarbazine Investigator's Choice: Ipilimumab Investigator's Choice: Pembrolizumab
Hide Arm/Group Description Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter. Dacarbazine administered at 1,000 mg/m^2 of body surface area IV infusion every 3 weeks until confirmed disease progression or unacceptable toxicity. Ipilimumab administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments. Pembrolizumab administered at 2 mg/kg IV infusion 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.
Period Title: Overall Study
Started 252 7 16 103
Completed 0 0 10 0
Not Completed 252 7 6 103
Reason Not Completed
Not Treated             7             0             3             12
Death             3             0             0             1
Withdrawal by Subject             7             0             0             3
Physician Decision             1             0             0             2
Progressive Disease             154             6             2             70
Adverse Event             6             1             1             3
Alternate anticancer treatment             1             0             0             1
Ongoing             73             0             0             11
Arm/Group Title Tebentafusp Investigator's Choice Total
Hide Arm/Group Description Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter. 1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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. Total of all reporting groups
Overall Number of Baseline Participants 252 126 378
Hide Baseline Analysis Population Description
The Intent-to-treat (ITT) Analysis Set comprises all participants assigned to treatment analyzed by the treatment assignment whether or not the participant received the assigned treatment. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 252 participants 126 participants 378 participants
61.3  (11.9) 63.6  (10.7) 62.1  (11.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 252 participants 126 participants 378 participants
Female
124
  49.2%
64
  50.8%
188
  49.7%
Male
128
  50.8%
62
  49.2%
190
  50.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 252 participants 126 participants 378 participants
American Indian or Alaska Native
0
   0.0%
1
   0.8%
1
   0.3%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
222
  88.1%
107
  84.9%
329
  87.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
30
  11.9%
18
  14.3%
48
  12.7%
1.Primary Outcome
Title Efficacy: Overall Survival
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Analysis Set comprises all participants assigned to treatment analyzed by the treatment assignment whether or not the participant received the assigned treatment. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design; therefore, data per different treatments were not analyzed.
Arm/Group Title Tebentafusp Investigator's Choice
Hide Arm/Group Description:
Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.
1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
Overall Number of Participants Analyzed 252 126
Median (95% Confidence Interval)
Unit of Measure: Months
21.7
(18.6 to 28.6)
16.0
(9.7 to 18.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tebentafusp, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.37 to 0.71
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Safety: Number of Participants With Treatment Emergent Adverse Events
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set includes all randomized participants who received at least 1 full or partial dose of tebentafusp or investigator's choice. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design; therefore, data per different treatments were not analyzed.
Arm/Group Title Tebentafusp Investigator's Choice
Hide Arm/Group Description:
Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.
1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
Overall Number of Participants Analyzed 245 111
Measure Type: Count of Participants
Unit of Measure: Participants
245
 100.0%
105
  94.6%
3.Secondary Outcome
Title Efficacy: Progression Free Survival (PFS)
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Analysis Set comprises all participants assigned to treatment analyzed by the treatment assignment whether or not the participant received the assigned treatment. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design; therefore, data per different treatments were not analyzed.
Arm/Group Title Tebentafusp Investigator's Choice
Hide Arm/Group Description:
Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.
1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
Overall Number of Participants Analyzed 252 126
Median (95% Confidence Interval)
Unit of Measure: Months
3.3
(3.0 to 5.0)
2.9
(2.8 to 3.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tebentafusp, Investigator's Choice
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0139
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.58 to 0.94
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Quality-of-Life: Change From Baseline in EQ-5D,5L Domain Scores
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Analysis Set comprises all participants assigned to treatment analyzed by the treatment assignment whether or not the participant received the assigned treatment. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design; therefore, data per different treatments were not analyzed.
Arm/Group Title Tebentafusp Investigator's Choice
Hide Arm/Group Description:
Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.
1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
Overall Number of Participants Analyzed 252 126
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Mobility - Baseline Cycle 1 Number Analyzed 194 participants 78 participants
1.2  (0.62) 1.3  (0.55)
Mobility - Change at Cycle 3 Number Analyzed 136 participants 45 participants
-0.1  (0.66) 0.1  (0.47)
Mobility - Change at Cycle 5 Number Analyzed 108 participants 28 participants
0.0  (0.73) 0.3  (0.65)
Mobility - Change at Cycle 9 Number Analyzed 71 participants 14 participants
0.0  (0.91) 0.0  (0.55)
Mobility - Change at Cycle 13 Number Analyzed 47 participants 9 participants
-0.1  (0.60) 0.3  (0.87)
Mobility - Change at Cycle 17 Number Analyzed 22 participants 6 participants
0.3  (0.57) 0.2  (0.41)
Mobility - Change at Cycle 21 Number Analyzed 13 participants 2 participants
0.0  (0.58) 0.5  (0.71)
Mobility - Change at Cycle 25 Number Analyzed 8 participants 1 participants
0.1  (0.64) 0.0  (0.00)
Mobility - Change at Cycle 29 Number Analyzed 9 participants 2 participants
0.0  (0.50) 0.0  (0.00)
Mobility - Change at EOT Number Analyzed 95 participants 45 participants
0.3  (0.73) 0.4  (0.99)
Self-care - Baseline Cycle 1 Number Analyzed 194 participants 78 participants
1.1  (0.45) 1.1  (0.29)
Self-care - Change at Cycle 3 Number Analyzed 136 participants 45 participants
0.0  (0.49) 0.0  (0.26)
Self-care - Change at Cycle 5 Number Analyzed 108 participants 28 participants
0.0  (0.42) 0.0  (0.00)
Self-care - Change at Cycle 9 Number Analyzed 71 participants 14 participants
0.0  (0.58) 0.0  (0.00)
Self-care - Change at Cycle 13 Number Analyzed 47 participants 9 participants
0.1  (0.52) 0.1  (0.33)
Self-care - Change at Cycle 17 Number Analyzed 22 participants 6 participants
0.1  (0.68) 0.0  (0.00)
Self-care - Change at Cycle 21 Number Analyzed 13 participants 2 participants
0.0  (0.00) 0.0  (0.00)
Self-care - Change at Cycle 25 Number Analyzed 8 participants 1 participants
0.0  (0.00) 0.0  (0.00)
Self-care - Change at Cycle 29 Number Analyzed 9 participants 2 participants
0.0  (0.00) 0.0  (0.00)
Self-care - Change at EOT Number Analyzed 95 participants 45 participants
0.1  (0.60) 0.1  (0.56)
Usual activities - Baseline Cycle 1 Number Analyzed 194 participants 78 participants
1.2  (0.53) 1.3  (0.55)
Usual activities - Change at Cycle 3 Number Analyzed 136 participants 45 participants
0.2  (0.59) 0.1  (0.73)
Usual activities - Change at Cycle 5 Number Analyzed 108 participants 28 participants
0.1  (0.61) 0.2  (0.61)
Usual activities - Change at Cycle 9 Number Analyzed 71 participants 14 participants
0.2  (0.87) 0.1  (0.53)
Usual activities - Change at Cycle 13 Number Analyzed 47 participants 9 participants
0.3  (0.79) 0.1  (0.60)
Usual activities - Change at Cycle 17 Number Analyzed 22 participants 6 participants
0.5  (0.80) 0.2  (0.41)
Usual activities - Change at Cycle 21 Number Analyzed 13 participants 2 participants
0.3  (0.48) 0.0  (0.00)
Usual activities - Change at Cycle 25 Number Analyzed 8 participants 1 participants
0.3  (0.46) 0.0  (0.00)
Usual activities - Change at Cycle 29 Number Analyzed 9 participants 2 participants
0.2  (0.44) 0.0  (0.00)
Usual activities - Change at EOT Number Analyzed 95 participants 45 participants
0.4  (0.77) 0.5  (0.87)
Pain/Discomfort - Baseline Cycle 1 Number Analyzed 194 participants 78 participants
1.5  (0.71) 1.5  (0.73)
Pain/Discomfort - Change at Cycle 3 Number Analyzed 136 participants 45 participants
0.0  (0.75) 0.1  (0.73)
Pain/Discomfort - Change at Cycle 5 Number Analyzed 108 participants 28 participants
0.0  (0.65) 0.2  (0.72)
Pain/Discomfort - Change at Cycle 9 Number Analyzed 71 participants 14 participants
0.1  (0.73) -0.1  (0.73)
Pain/Discomfort - Change at Cycle 13 Number Analyzed 47 participants 9 participants
0.1  (0.51) 0.1  (0.93)
Pain/Discomfort - Change at Cycle 17 Number Analyzed 22 participants 6 participants
0.4  (0.85) 0.3  (0.52)
Pain/Discomfort - Change at Cycle 21 Number Analyzed 13 participants 2 participants
0.2  (0.55) 0.0  (0.00)
Pain/Discomfort - Change at Cycle 25 Number Analyzed 8 participants 1 participants
0.0  (0.53) 1.0 [1]   (NA)
Pain/Discomfort - Change at Cycle 29 Number Analyzed 9 participants 2 participants
0.1  (0.60) 0.5  (0.71)
Pain/Discomfort - Change at EOT Number Analyzed 95 participants 45 participants
0.2  (0.87) 0.4  (1.10)
Anxiety/Depression - Baseline Cycle 1 Number Analyzed 194 participants 78 participants
1.8  (0.94) 1.7  (0.89)
Anxiety/Depression - Change at Cycle 3 Number Analyzed 136 participants 45 participants
-0.2  (0.77) -0.3  (0.55)
Anxiety/Depression - Change at Cycle 5 Number Analyzed 108 participants 28 participants
-0.2  (0.74) 0.0  (0.61)
Anxiety/Depression - Change at Cycle 9 Number Analyzed 71 participants 14 participants
-0.3  (0.80) 0.1  (0.77)
Anxiety/Depression - Change at Cycle 13 Number Analyzed 47 participants 9 participants
-0.4  (0.77) -0.1  (0.60)
Anxiety/Depression - Change at Cycle 17 Number Analyzed 22 participants 6 participants
-0.4  (0.85) 0.0  (0.00)
Anxiety/Depression - Change at Cycle 21 Number Analyzed 13 participants 2 participants
-0.5  (0.88) 0.0  (0.00)
Anxiety/Depression - Change at Cycle 25 Number Analyzed 8 participants 1 participants
-0.4  (0.74) 0.0 [1]   (NA)
Anxiety/Depression - Change at Cycle 29 Number Analyzed 9 participants 2 participants
-0.6  (0.88) 0.5  (0.71)
Anxiety/Depression - Change at EOT Number Analyzed 95 participants 45 participants
0.3  (0.94) 0.2  (1.07)
[1]
Not calculable due to single participant.
5.Secondary Outcome
Title Quality-of-life: Change From Baseline in EQ-5D Visual Analogue Score (VAS)
Hide Description 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Analysis Set comprises all participants assigned to treatment analyzed by the treatment assignment whether or not the participant received the assigned treatment. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design; therefore, data per different treatments were not analyzed.
Arm/Group Title Tebentafusp Investigator's Choice
Hide Arm/Group Description:
Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.
1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
Overall Number of Participants Analyzed 252 126
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline Cycle 1 Number Analyzed 194 participants 78 participants
81.0  (16.36) 80.4  (18.31)
Change at Cycle 3 Number Analyzed 136 participants 45 participants
0.4  (14.69) -0.8  (14.28)
Change at Cycle 5 Number Analyzed 108 participants 28 participants
0.6  (15.61) -0.7  (14.38)
Change at Cycle 9 Number Analyzed 71 participants 14 participants
-0.9  (19.81) -3.3  (13.30)
Change at Cycle 13 Number Analyzed 47 participants 9 participants
-2.0  (16.48) -2.6  (8.37)
Change at Cycle 17 Number Analyzed 22 participants 6 participants
-10.2  (20.93) -8.5  (33.82)
Change at Cycle 21 Number Analyzed 13 participants 2 participants
-1.8  (14.52) -1.0  (5.66)
Change at Cycle 25 Number Analyzed 8 participants 1 participants
-13.6  (19.43) -4.0 [1]   (NA)
Change at Cycle 29 Number Analyzed 9 participants 2 participants
0.0  (9.25) -2.0  (1.41)
Change at EOT Number Analyzed 95 participants 45 participants
-10.1  (22.53) -11.7  (21.40)
[1]
Not calculable due to single participant
6.Secondary Outcome
Title Quality-of-Life: Change From Baseline in EORTC QLQ-C30 Global Health Status
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Analysis Set comprises all participants assigned to treatment analyzed by the treatment assignment whether or not the participant received the assigned treatment. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design; therefore, data per different treatments were not analyzed.
Arm/Group Title Tebentafusp Investigator's Choice
Hide Arm/Group Description:
Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.
1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
Overall Number of Participants Analyzed 252 126
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline Cycle 1 Number Analyzed 173 participants 65 participants
76.108  (20.233) 74.872  (20.439)
Change at Cycle 3 Number Analyzed 105 participants 35 participants
0.952  (16.274) -0.238  (14.919)
Change at Cycle 5 Number Analyzed 94 participants 22 participants
-1.152  (20.797) -10.227  (22.557)
Change at Cycle 9 Number Analyzed 57 participants 13 participants
-2.193  (19.577) -8.333  (13.176)
Change at Cycle 13 Number Analyzed 40 participants 9 participants
-5.625  (17.641) -10.185  (16.017)
Change at Cycle 17 Number Analyzed 18 participants 6 participants
-10.185  (28.087) -4.167  (6.972)
Change at Cycle 21 Number Analyzed 11 participants 2 participants
0.758  (18.429) -4.167  (5.893)
Change at Cycle 25 Number Analyzed 7 participants 1 participants
-2.381  (27.936) 0.00  (0.00)
Change at Cycle 29 Number Analyzed 6 participants 1 participants
-8.333  (19.720) 0.00  (0.00)
Change at EOT Number Analyzed 76 participants 34 participants
-10.417  (20.911) -10.539  (23.148)
7.Secondary Outcome
Title Pharmacokinetics (PK): Tebentafusp Concentration
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Analysis Set included participants in the Safety Analysis Set who had at least 1 measurable PK concentration and who had relevant date, time, and dosing data for the sample.
Arm/Group Title Tebentafusp
Hide Arm/Group Description:
Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.
Overall Number of Participants Analyzed 231
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: pg/mL
Cycle 1 Day 1 - End of Infusion Number Analyzed 207 participants
4201.929
(0.6%)
Cycle 1 Day 1 - 12 to 24 hours post-infusion Number Analyzed 212 participants
505.100
(0.7%)
Cycle 1 Day 8 - End of Infusion Number Analyzed 200 participants
5787.139
(0.4%)
Cycle 1 Day 8 - 12 to 24 hours post-infusion Number Analyzed 198 participants
738.602
(0.7%)
Cycle 1 Day 15 - End of Infusion Number Analyzed 202 participants
13715.914
(0.5%)
Cycle 1 Day 15 - 12 to 24 hours post-infusion Number Analyzed 205 participants
1685.354
(0.6%)
8.Secondary Outcome
Title Efficacy: Objective Response Rate (ORR)
Hide Description 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.
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Efficacy: Duration of Response (DOR)
Hide Description 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.
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Efficacy: Disease Control Rate (DCR)
Hide Description 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.
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Pharmacokinetics: Frequency of Anti-IMCgp100 Antibody Formation
Hide Description [Not Specified]
Time Frame Approximately 5 assessments will be performed between first dose of IMCgp100 and end of treatment, assessed up to 5.5 years.
Outcome Measure Data Not Reported
Time Frame Approximately 36 months.
Adverse Event Reporting Description The Safety Analysis Set included all randomized participants who received at least 1 full or partial dose of tebentafusp or investigator's choice. Combining participants into a single group (Investigator's Choice) was pre-specified as part of the study design and data for each treatment in that arm were not analyzed separately. Adverse events were defined as events that were new or worsened during the on-treatment period.
 
Arm/Group Title Tebentafusp Investigator's Choice
Hide Arm/Group Description Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter. 1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
All-Cause Mortality
Tebentafusp Investigator's Choice
Affected / at Risk (%) Affected / at Risk (%)
Total   84/245 (34.29%)      57/111 (51.35%)    
Hide Serious Adverse Events
Tebentafusp Investigator's Choice
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   69/245 (28.16%)      26/111 (23.42%)    
Blood and lymphatic system disorders     
Anemia * 1  1/245 (0.41%)  2 0/111 (0.00%)  0
Cardiac disorders     
Left ventricular dysfunction * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Endocrine disorders     
Hypopituitarism * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Eye disorders     
Diplopia * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Periorbital edema * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Uveitis * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Gastrointestinal disorders     
Abdominal pain * 1  2/245 (0.82%)  4 3/111 (2.70%)  3
Abdominal pain upper * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Colitis * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Diarrhea * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Enteritis * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Gastritis * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Nausea * 1  4/245 (1.63%)  6 1/111 (0.90%)  2
Vomiting * 1  2/245 (0.82%)  3 0/111 (0.00%)  0
General disorders     
Asthenia * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Fatigue * 1  1/245 (0.41%)  3 0/111 (0.00%)  0
Gait disturbance * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
General physical health deterioration * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Pyrexia * 1  6/245 (2.45%)  6 2/111 (1.80%)  2
Hepatobiliary disorders     
Biliary obstruction * 1  1/245 (0.41%)  3 0/111 (0.00%)  0
Hepatic failure * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Hepatic necrosis * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Hepatic pain * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Hepatomegaly * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Hepatotoxicity * 1  2/245 (0.82%)  18 0/111 (0.00%)  0
Hyperbilirubinemia * 1  2/245 (0.82%)  3 3/111 (2.70%)  5
Hypertransaminasemia * 1  1/245 (0.41%)  5 0/111 (0.00%)  0
Immune system disorders     
Anaphylactic reaction * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Cytokine release syndrome * 1  24/245 (9.80%)  51 0/111 (0.00%)  0
Infections and infestations     
Anorectal infection * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Appendicitis * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
COVID-19 * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Erysipelas * 1  1/245 (0.41%)  2 0/111 (0.00%)  0
Pneumonia * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Pneumonia mycoplasmal * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Salmonella sepsis * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Injury, poisoning and procedural complications     
Fall * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Procedural pain * 1  1/245 (0.41%)  1 1/111 (0.90%)  1
Investigations     
Alanine aminotransferase increased * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Amylase increased * 1  1/245 (0.41%)  2 0/111 (0.00%)  0
Aspartate aminotransferase increased * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Blood creatinine increased * 1  2/245 (0.82%)  2 0/111 (0.00%)  0
Lipase increased * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Metabolism and nutrition disorders     
Dehydration * 1  0/245 (0.00%)  0 2/111 (1.80%)  2
Hyperglycemia * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Tumor lysis syndrome * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Bone pain * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Pathological fracture * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Meningioma * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Metastases to abdominal cavity * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Neoplasm progression * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Tumor pain * 1  2/245 (0.82%)  3 0/111 (0.00%)  0
Nervous system disorders     
Brain edema * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Dizziness * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Intracranial mass * 1  0/245 (0.00%)  0 1/111 (0.90%)  2
Lethargy * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Motor dysfunction * 1  1/245 (0.41%)  2 0/111 (0.00%)  0
Presyncope * 1  1/245 (0.41%)  2 0/111 (0.00%)  0
Seizure * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Spinal cord compression * 1  1/245 (0.41%)  2 0/111 (0.00%)  0
Psychiatric disorders     
Mental status changes * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury * 1  1/245 (0.41%)  2 0/111 (0.00%)  0
Renal failure * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Reproductive system and breast disorders     
Scrotal inflammation * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Cough * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Dyspnea * 1  2/245 (0.82%)  2 0/111 (0.00%)  0
Pleurisy * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Pneumonitis * 1  0/245 (0.00%)  0 1/111 (0.90%)  2
Pulmonary embolism * 1  1/245 (0.41%)  2 3/111 (2.70%)  4
Pulmonary edema * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Sleep apnea syndrome * 1  0/245 (0.00%)  0 1/111 (0.90%)  1
Skin and subcutaneous tissue disorders     
Pruritus * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Rash * 1  6/245 (2.45%)  10 0/111 (0.00%)  0
Rash maculo-papular * 1  4/245 (1.63%)  13 0/111 (0.00%)  0
Rash papular * 1  1/245 (0.41%)  2 0/111 (0.00%)  0
Skin reaction * 1  1/245 (0.41%)  1 0/111 (0.00%)  0
Urticaria * 1  1/245 (0.41%)  2 0/111 (0.00%)  0
Vascular disorders     
Hypotension * 1  5/245 (2.04%)  6 0/111 (0.00%)  0
1
Term from vocabulary, MedDRA 23.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tebentafusp Investigator's Choice
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   245/245 (100.00%)      102/111 (91.89%)    
Blood and lymphatic system disorders     
Anemia * 1  25/245 (10.20%)  62 4/111 (3.60%)  4
Lymphopenia * 1  24/245 (9.80%)  51 3/111 (2.70%)  4
Thrombocytopenia * 1  5/245 (2.04%)  7 6/111 (5.41%)  10
Cardiac disorders     
Tachycardia * 1  24/245 (9.80%)  45 3/111 (2.70%)  3
Endocrine disorders     
Hyperthyroidism * 1  2/245 (0.82%)  2 13/111 (11.71%)  16
Hypothyroidism * 1  3/245 (1.22%)  3 12/111 (10.81%)  15
Eye disorders     
Periorbital edema * 1  26/245 (10.61%)  51 1/111 (0.90%)  1
Gastrointestinal disorders     
Abdominal pain * 1  59/245 (24.08%)  92 14/111 (12.61%)  21
Abdominal pain upper * 1  50/245 (20.41%)  79 14/111 (12.61%)  21
Constipation * 1  44/245 (17.96%)  65 13/111 (11.71%)  15
Diarrhea * 1  61/245 (24.90%)  120 22/111 (19.82%)  45
Dry mouth * 1  8/245 (3.27%)  9 6/111 (5.41%)  6
Dyspepsia * 1  20/245 (8.16%)  28 5/111 (4.50%)  5
Nausea * 1  119/245 (48.57%)  288 28/111 (25.23%)  44
Vomiting * 1  73/245 (29.80%)  163 10/111 (9.01%)  19
General disorders     
Asthenia * 1  38/245 (15.51%)  71 9/111 (8.11%)  11
Chills * 1  117/245 (47.76%)  378 4/111 (3.60%)  4
Face edema * 1  25/245 (10.20%)  39 2/111 (1.80%)  2
Fatigue * 1  124/245 (50.61%)  352 39/111 (35.14%)  53
Influenza like illness * 1  18/245 (7.35%)  75 2/111 (1.80%)  2
Edema peripheral * 1  66/245 (26.94%)  119 3/111 (2.70%)  3
Pyrexia * 1  186/245 (75.92%)  682 7/111 (6.31%)  11
Hepatobiliary disorders     
Hepatic pain * 1  15/245 (6.12%)  41 4/111 (3.60%)  4
Hyperbilirubinemia * 1  26/245 (10.61%)  56 6/111 (5.41%)  6
Immune system disorders     
Cytokine release syndrome * 1  34/245 (13.88%)  91 0/111 (0.00%)  0
Infections and infestations     
Nasopharyngitis * 1  20/245 (8.16%)  24 1/111 (0.90%)  1
Urinary tract infection * 1  14/245 (5.71%)  19 5/111 (4.50%)  5
Investigations     
Alanine aminotransferase increased * 1  50/245 (20.41%)  127 12/111 (10.81%)  19
Aspartate aminotransferase increased * 1  55/245 (22.45%)  134 11/111 (9.91%)  19
Blood alkaline phosphatase increased * 1  23/245 (9.39%)  60 3/111 (2.70%)  4
Blood creatinine increased * 1  13/245 (5.31%)  26 3/111 (2.70%)  3
Blood lactate dehydrogenase increased * 1  13/245 (5.31%)  20 3/111 (2.70%)  8
Lipase increased * 1  35/245 (14.29%)  73 7/111 (6.31%)  12
Weight decreased * 1  16/245 (6.53%)  16 7/111 (6.31%)  11
Metabolism and nutrition disorders     
Decreased appetite * 1  45/245 (18.37%)  56 15/111 (13.51%)  17
Hypokalemia * 1  18/245 (7.35%)  24 3/111 (2.70%)  3
Hypomagnesemia * 1  19/245 (7.76%)  31 1/111 (0.90%)  1
Hypophosphatemia * 1  27/245 (11.02%)  52 2/111 (1.80%)  5
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  53/245 (21.63%)  97 18/111 (16.22%)  30
Back pain * 1  45/245 (18.37%)  56 9/111 (8.11%)  14
Muscle spasms * 1  14/245 (5.71%)  30 0/111 (0.00%)  0
Myalgia * 1  24/245 (9.80%)  40 7/111 (6.31%)  9
Pain in extremity * 1  24/245 (9.80%)  36 3/111 (2.70%)  3
Nervous system disorders     
Dizziness * 1  26/245 (10.61%)  46 9/111 (8.11%)  12
Headache * 1  75/245 (30.61%)  135 11/111 (9.91%)  15
Parasthesia * 1  27/245 (11.02%)  53 1/111 (0.90%)  1
Psychiatric disorders     
Anxiety * 1  13/245 (5.31%)  14 2/111 (1.80%)  2
Insomnia * 1  22/245 (8.98%)  24 6/111 (5.41%)  6
Respiratory, thoracic and mediastinal disorders     
Cough * 1  44/245 (17.96%)  67 11/111 (9.91%)  12
Dyspnea * 1  31/245 (12.65%)  42 7/111 (6.31%)  7
Oropharyngeal pain * 1  16/245 (6.53%)  20 1/111 (0.90%)  1
Skin and subcutaneous tissue disorders     
Alopecia * 1  21/245 (8.57%)  22 2/111 (1.80%)  2
Dry skin * 1  77/245 (31.43%)  106 4/111 (3.60%)  4
Erythema * 1  60/245 (24.49%)  120 1/111 (0.90%)  1
Hair color changes * 1  48/245 (19.59%)  62 0/111 (0.00%)  0
Night sweats * 1  13/245 (5.31%)  17 1/111 (0.90%)  1
Pruritus * 1  168/245 (68.57%)  536 26/111 (23.42%)  33
Rash * 1  132/245 (53.88%)  603 18/111 (16.22%)  25
Rash maculo-papular * 1  75/245 (30.61%)  343 9/111 (8.11%)  10
Skin exfoliation * 1  51/245 (20.82%)  80 2/111 (1.80%)  2
Skin hyperpigmentation * 1  19/245 (7.76%)  24 2/111 (1.80%)  2
Skin hypopigmentation * 1  22/245 (8.98%)  26 2/111 (1.80%)  2
Vitiligo * 1  40/245 (16.33%)  45 4/111 (3.60%)  5
Vascular disorders     
Flushing * 1  25/245 (10.20%)  34 1/111 (0.90%)  2
Hypertension * 1  38/245 (15.51%)  91 8/111 (7.21%)  8
Hypotension * 1  91/245 (37.14%)  212 3/111 (2.70%)  4
1
Term from vocabulary, MedDRA 23.1
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Immunocore, Ltd
Phone: 1-844-IMMUNO-1
EMail: clinicaltrials@immunocore.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Immunocore Ltd
ClinicalTrials.gov Identifier: NCT03070392    
Other Study ID Numbers: IMCgp100-202
First Submitted: February 14, 2017
First Posted: March 3, 2017
Results First Submitted: August 17, 2021
Results First Posted: September 14, 2021
Last Update Posted: March 21, 2022