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Study to Assess the Tolerability of a Bispecific Targeted Biologic IMCgp100 in Malignant 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: NCT01211262
Recruitment Status : Completed
First Posted : September 29, 2010
Results First Posted : July 8, 2020
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Immunocore Ltd

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malignant Melanoma
Intervention Drug: IMCgp100
Enrollment 84
Recruitment Details  
Pre-assignment Details All-patients population and safety population both comprised 84 participants who enrolled in the study and who also received at least one IMCgp100 dose; the all-patients and safety population for Arm 1 was 66 participants and for Arm 2 was 18 participants. Efficacy population was 54 participants in Arm 1 and 15 participants in Arm 2.
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each. Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Period Title: Overall Study
Started 66 18
Completed 43 8
Not Completed 23 10
Reason Not Completed
Progressive Disease             18             9
Adverse Event             4             0
Withdrawal of Consent             1             0
Other             0             1
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen Total
Hide Arm/Group Description Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each. Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle Total of all reporting groups
Overall Number of Baseline Participants 66 18 84
Hide Baseline Analysis Population Description
Safety population: The all-patients population and the safety population both comprised the 84 participants who enrolled in the study and who also received at least one IMCgp100 dose.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 66 participants 18 participants 84 participants
58.2
(25 to 78)
60.4
(31 to 75)
58.7
(25 to 78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 18 participants 84 participants
Female 25 5 30
Male 41 13 54
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 66 participants 18 participants 84 participants
White 62 17 79
Black 1 0 1
Asian 1 0 1
Other 2 1 3
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) of IMCgp100 Administered Weekly (Dose Escalation Part)
Hide Description

The maximum tolerated dose (MTD) for IMCgp100 administered by weekly dosing was determined based on the frequency of dose-limiting toxicity (DLT) occurring during Days 1 to 8. Participants presented at MTD in the dose escalation phase.

Abbreviations: ng/kg=nanograms/kilogram

Time Frame Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: all participants who received at least 1 dose of IMCgp100, up to a maximum of 600 ng/kg.
Arm/Group Title IMCgp100 Weekly Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 27
Measure Type: Number
Unit of Measure: ng/kg
600
2.Primary Outcome
Title MTD of IMCgp100 Administered Daily (Dose Escalation Part)
Hide Description

The MTD for IMCgp100 administered by daily dosing was determined based on the frequency of DLT occurring during Days 1 to 8. The 50 mcg dose was the RP2D for daily dosing, as the MTD was not achieved.

Abbreviations: mcg=micrograms

Time Frame Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: all participants who received at least 1 dose of IMCgp100
Arm/Group Title IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Daily intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: mcg
50
3.Primary Outcome
Title Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
Hide Description Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) with an onset date after the date of first dose and within 30 days after the last administration of study medication in either treatment arm. AEs with missing date of onset were considered treatment emergent.
Time Frame Day 1 (first dose), 30 days after the last dose
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Overall Number of Participants Analyzed 66 18
Measure Type: Number
Unit of Measure: percentage of participants
100.0 100.00
4.Primary Outcome
Title Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology)
Hide Description Laboratory parameters included clinical chemistry, hematology, and urinalysis. For hematology, this included red cell count, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, leukocyte differential count (percentage or absolute), prothrombin time, and activated partial tissue thromboplastin time. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.
Time Frame 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment.
Overall Number of Participants Analyzed 66 18
Measure Type: Number
Unit of Measure: number of participants
Lymphocytes 12 1
Hemoglobin 1 2
Neutrophils 1 0
CD4 Cells 1 0
Leukocytes 1 0
5.Primary Outcome
Title Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology)
Hide Description Laboratory parameters included clinical chemistry, hematology, and urinalysis. For hematology, this included red cell count, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, leukocyte differential count (percentage or absolute), prothrombin time, and activated partial tissue thromboplastin time. Laboratory parameter abnormalities were graded by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.
Time Frame 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Overall Number of Participants Analyzed 66 18
Measure Type: Number
Unit of Measure: number of participants
Lymphocytes-Grade 3 Number Analyzed 61 participants 16 participants
15 2
Lymphocytes-Grade 4 Number Analyzed 61 participants 16 participants
2 2
CD4 Count-Grade 3 Number Analyzed 32 participants 1 participants
4 1
CD4 Count-Grade 4 Number Analyzed 32 participants 1 participants
4 1
Hemoglobin-Grade 3 Number Analyzed 63 participants 17 participants
0 3
Leukocytes-Grade 3 Number Analyzed 65 participants 17 participants
1 0
6.Primary Outcome
Title Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry)
Hide Description Laboratory parameters included clinical chemistry, hematology, and urinalysis. Clinical chemistry parameters included calcium, phosphorus, magnesium, albumin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase, sodium, potassium, bicarbonate, creatinine, chloride, glucose, urea, uric acid, and C-reactive protein. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.
Time Frame 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Overall Number of Participants Analyzed 66 18
Measure Type: Number
Unit of Measure: number of participants
Albumin 3 3
Alkaline Phosphatase 3 1
Aspartate Aminotransferase 1 2
Alanine Aminotransferase 1 1
Potassium 1 1
Calcium 0 1
Glucose 1 0
Magnesium 0 1
Sodium 0 1
Uric Acid 1 0
7.Primary Outcome
Title Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry)
Hide Description Laboratory parameters included clinical chemistry, hematology, and urinalysis. Clinical chemistry parameters included calcium, phosphorus, magnesium, albumin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase, sodium, potassium, bicarbonate, creatinine, chloride, glucose, urea, uric acid, and C-reactive protein. Laboratory parameter abnormalities were graded by the investigator using CTCAE v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.
Time Frame 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Overall Number of Participants Analyzed 66 18
Measure Type: Number
Unit of Measure: number of participants
Sodium-Grade 3 Number Analyzed 62 participants 18 participants
2 4
Potassium-Grade 3 Number Analyzed 62 participants 17 participants
2 1
Glucose-Grade 3 Number Analyzed 63 participants 17 participants
1 1
Aspartate Aminotransferase-Grade 3 Number Analyzed 63 participants 18 participants
1 0
Calcium-Grade 3 Number Analyzed 64 participants 18 participants
0 1
8.Primary Outcome
Title Number of Participants Experiencing Clinically Significant Electrocardiograms (ECGs)
Hide Description Twelve lead ECGs were obtained after the participant has rested in a supine position for at least 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator or designated physician occurring at any time on treatment from normal pre-dose.
Time Frame 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Overall Number of Participants Analyzed 66 18
Measure Type: Number
Unit of Measure: number of participants
3 0
9.Primary Outcome
Title Number of Participants Experiencing Clinically Significant Vital Signs
Hide Description Vital signs included temperature, blood pressure, respiration rate, and heart rate. Measurements were made after the participant had been resting supine for a minimum of 5 minutes. Blood pressure and heart rate were measured using a recording device with an appropriate cuff size. Temperature and respiration rate were measured as per clinical practice. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.
Time Frame 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Overall Number of Participants Analyzed 66 18
Measure Type: Number
Unit of Measure: number of participants
High Systolic Blood Pressure 17 2
Low Systolic Blood Pressure 8 5
High Diastolic Blood Pressure 20 3
Low Diastolic Blood Pressure 37 12
High Heart Rate 34 12
Low Heart Rate 8 1
High Temperature 33 13
10.Primary Outcome
Title Number of Participants Experiencing Clinically Significant Physical Examination Results (Weight Decrease)
Hide Description Physical examination included weight, a record of skin pigmentation, and photographic record of any vitiligo if present. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.
Time Frame 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Overall Number of Participants Analyzed 66 18
Measure Type: Number
Unit of Measure: number of participants
3 1
11.Primary Outcome
Title Number of Participants Experiencing ≥Grade 3 Severity in Physical Examination Results (Skin Pigmentation)
Hide Description Physical examination included weight, a record of skin pigmentation, and photographic record of any vitiligo if present. Abnormalities were graded by the investigator using CTCAE v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.
Time Frame 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Overall Number of Participants Analyzed 66 18
Measure Type: Number
Unit of Measure: number of participants
0 0
12.Secondary Outcome
Title Number of Participants With Best Overall Response Per Response Evaluation Criteria In Solid Tumors (RECIST) (Weekly Dosing-Dose Expansion Part)
Hide Description The best overall response was assigned as complete response (CR), partial response (PR), minor response, stable disease, progressive disease (PD) or not evaluable (NE) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Time Frame 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population: only evaluable participants (those having both a baseline and post treatment sample).
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Overall Number of Participants Analyzed 54 15
Measure Type: Number
Unit of Measure: participants
5 1
13.Secondary Outcome
Title Number of Participants With Anti-IMCgp100 Antibody Formation (Dose Escalation and Dose Expansion Parts)
Hide Description To provide a comprehensive anti-drug antibody (ADA) summary for the study, individual participant data were combined and assessed as distinct groups based on characteristics of their ADA response. Evaluable participants were those with post-drug administration samples. ADA prevalence (pre- existing antibody response) was measured as the number of baseline-positive participant out of all participants who provided baseline samples. Overall ADA incidence was calculated based on the combined number of treatment-boosted and treatment-induced ADA-positive participants. The treatment-induced incidence was determined as the number of ADA- positive participants of those that were ADA-negative at baseline; while treatment-boosted incidence was determined as the number of participants with an ADA titer increase equal to or greater than the minimum significant dilution (3-fold) of the assay.
Time Frame 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Overall Number of Participants Analyzed 66 18
Measure Type: Number
Unit of Measure: participants
2 1
14.Secondary Outcome
Title Estimated Maximum Plasma Concentration (Cmax) of IMCgp100 By-weight Doses (Dose Escalation)
Hide Description The maximum plasma concentration (Cmax) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. Abbreviations: ng/kg = nanograms/kilogram
Time Frame Day 1, Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics (PK) Population: all participants who receive at least 1 dose of IMCgp100 and have at least 1 measurable PK concentration with the relevant date, time and dosing data for this sample.
Arm/Group Title IMCgp100 Weekly Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 42
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: picograms/milliliter
15 ng/kg by-weight dose Number Analyzed 3 participants
305.50
(583.47%)
45 ng/kg by-weight dose Number Analyzed 3 participants
271.33
(21.49%)
135 ng/kg by-weight dose Number Analyzed 3 participants
371.79
(57.25%)
270 ng/kg by-weight dose Number Analyzed 3 participants
856.35
(41.01%)
405 ng/kg by-weight dose Number Analyzed 6 participants
2345.25
(35.74%)
600 ng/kg by-weight dose Number Analyzed 20 participants
6188.54
(41.21%)
900 ng/kg by-weight dose Number Analyzed 4 participants
8868.83
(27.92%)
15.Secondary Outcome
Title Estimated Cmax of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts)
Hide Description The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time Frame Day 1, Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: picograms/milliliter
8868.83
(27.92%)
16.Secondary Outcome
Title Estimated Cmax of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts)
Hide Description The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. Abbreviations: mcg = micrograms
Time Frame Day 1, Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 21
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: picograms/milliliter
20 mcg Number Analyzed 7 participants
3239.82
(20.97%)
40 mcg Number Analyzed 3 participants
8316.43
(45.10%)
50 mcg Number Analyzed 11 participants
8740.99
(38.01%)
17.Secondary Outcome
Title Estimated Cmax of IMCgp100 of 600 ng/kg By-weight Dose (Dose Escalation)
Hide Description The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time Frame Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: picograms/milliliter
Day 1 Number Analyzed 10 participants
7311  (1770)
Day 8 Number Analyzed 9 participants
5726  (3605)
Day 15 Number Analyzed 9 participants
6182  (1456)
Day 22 Number Analyzed 9 participants
6490  (2488)
Day 29 Number Analyzed 9 participants
6245  (3047)
Day 36 Number Analyzed 9 participants
6396  (3474)
Day 43 Number Analyzed 8 participants
6014  (1125)
Day 50 Number Analyzed 8 participants
7136  (2744)
18.Secondary Outcome
Title Estimated Cmax of IMCgp100 of 20/30/50 mcg Flat Dose (Dose Escalation)
Hide Description The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. On Day 1, IMCgp100 20 mcg was given, IMCgp100 30 mcg was administered on Day 8, and IMCgp100 50 mcg was dosed on Days 15 and after.
Time Frame Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: mcg
Day 1 Number Analyzed 7 participants
3299  (660)
Day 8 Number Analyzed 7 participants
5056  (1175)
Day 15 Number Analyzed 7 participants
7981  (2278)
Day 22 Number Analyzed 6 participants
6682  (1395)
Day 29 Number Analyzed 7 participants
4710  (3621)
Day 36 Number Analyzed 5 participants
7100  (1535)
Day 43 Number Analyzed 7 participants
7240  (1906)
Day 50 Number Analyzed 6 participants
6658  (1211)
19.Secondary Outcome
Title Estimated Cmax of IMCgp100 of 40/40/50 mcg Flat Dose (Dose Escalation)
Hide Description The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. This dosing regimen was implemented following the Urgent Safety Measure to adapt the dosing in the Phase 1 study that dropped Dose 1 to 40 mcg from the identified 50 mcg RP2D.
Time Frame Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: mcg
Day 1 Number Analyzed 3 participants
8847  (3811)
Day 8 Number Analyzed 2 participants
5340  (311)
Day 15 Number Analyzed 3 participants
8373  (2682)
Day 22 Number Analyzed 2 participants
7445  (983)
Day 29 Number Analyzed 2 participants
3288  (4614)
Day 36 Number Analyzed 3 participants
8073  (1337)
Day 43 Number Analyzed 2 participants
6735  (672)
Day 50 Number Analyzed 2 participants
7130  (4483)
20.Secondary Outcome
Title Estimated Cmax of IMCgp100 of 50 mcg Flat Dose (Dose Escalation)
Hide Description The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The RP2D identified in this study following review of all safety and pharmacokinetic data in the dose escalation of the Phase 1 study was the 50 mcg flat dose.
Time Frame Cycle 1: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: mcg
Day 1 Number Analyzed 11 participants
9327  (3802)
Day 8 Number Analyzed 8 participants
6414  (3653)
Day 15 Number Analyzed 10 participants
7236  (3304)
Day 22 Number Analyzed 10 participants
7620  (2710)
Day 29 Number Analyzed 9 participants
8186  (3178)
Day 36 Number Analyzed 10 participants
8425  (4594)
Day 43 Number Analyzed 9 participants
6905  (4097)
Day 50 Number Analyzed 9 participants
9018  (5001)
21.Secondary Outcome
Title Estimated Cmax of IMCgp100 of a Single Infusion Flat Dose (Dose Escalation)
Hide Description The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time Frame Cycle 1: Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description:
Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.
Overall Number of Participants Analyzed 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: picograms/milliliter
10 mcg Number Analyzed 3 participants
997.83
(38.01%)
20 mcg Number Analyzed 3 participants
3599.18
(15.42%)
30 mcg Number Analyzed 3 participants
3599.18
(15.42%)
40 mcg Number Analyzed 4 participants
6157.90
(29.52%)
50 mcg Number Analyzed 5 participants
8111.79
(27.80%)
22.Secondary Outcome
Title Area Under the Concentration-Time Curve (AUC) of IMCgp100 By-weight Dose (Dose Escalation)
Hide Description The area under the concentration-time curve (AUC), measured in hours by picograms per milliliter ( h*pg/ml) is a method of measurement of the total exposure of a drug in blood.
Time Frame Day 1, Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 42
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours * picograms/milliliter
15 ng/kg Number Analyzed 3 participants
5666.63
(434.62%)
45 ng/kg Number Analyzed 3 participants
2965.10
(49.17%)
135 ng/kg Number Analyzed 3 participants
2904.91
(96.95%)
270 ng/kg Number Analyzed 3 participants
10649.19
(40.82%)
405 ng/kg Number Analyzed 6 participants
33332.31
(43.57%)
600 ng/kg Number Analyzed 20 participants
63507.24
(43.97%)
900 ng/kg Number Analyzed 4 participants
97724.58
(29.49%)
23.Secondary Outcome
Title AUC of IMCgp100 of 900 ng/kg By-weight Dose (Dose Escalation and Dose Expansion Parts)
Hide Description The AUC, measured in h*pg/ml, is a method of measurement of the total exposure of a drug in blood.
Time Frame Day 1, Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours * picograms/milliliter
97724.58
(29.49%)
24.Secondary Outcome
Title AUC of IMCgp100 Flat Dose (Dose Escalation and Dose Expansion Parts)
Hide Description The AUC (measured in h*pg/ml) is a method of measurement of the total exposure of a drug in blood. Participants in the 20 mcg and 40 mcg dose groups received intra-participant dose-escalation up to 50 mcg on Day 15.
Time Frame Day 1, Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours * picograms/milliliter
20 mcg Number Analyzed 7 participants
3239.82
(20.97%)
40 mcg Number Analyzed 3 participants
59333.15
(21.44%)
25.Secondary Outcome
Title AUC of IMCgp100 of 50 mcg Flat Dose (Dose Escalation and Dose Expansion Parts)
Hide Description The AUC (measured in h*pg/ml) is a method of measurement of the total exposure of a drug in blood.
Time Frame Day 1, Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title IMCgp100 Weekly Dosing Regimen
Hide Arm/Group Description:
Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.
Overall Number of Participants Analyzed 11
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours * picograms/milliliter
73134.57
(55.88%)
Time Frame Up to Day 80 (follow up)
Adverse Event Reporting Description Adverse events were recorded from the time informed consent was obtained to 30 days after the final dose or 30 days after withdrawal from treatment. The safety population was comprised of the 84 participants who enrolled in the study and included all participants who received at least one dose of IMCgp100.
 
Arm/Group Title IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Hide Arm/Group Description Weekly intravenous (IV) infusions of IMCgp100 at the weekly maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) over treatment cycles of eight weeks each. Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six week treatment cycle at the MTD/daily RP2D.
All-Cause Mortality
IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Affected / at Risk (%) Affected / at Risk (%)
Total   8/66 (12.12%)      8/18 (44.44%)    
Hide Serious Adverse Events
IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/66 (36.36%)      5/18 (27.78%)    
Blood and lymphatic system disorders     
ANAEMIA  1  1/66 (1.52%)  1 0/18 (0.00%)  0
Cardiac disorders     
ATRIAL FIBRILLATION  1  0/66 (0.00%)  0 1/18 (5.56%)  1
Gastrointestinal disorders     
ABDOMINAL PAIN  1  1/66 (1.52%)  1 0/18 (0.00%)  0
ASCITES  1  1/66 (1.52%)  1 0/18 (0.00%)  0
INTESTINAL OBSTRUCTION  1  0/66 (0.00%)  0 1/18 (5.56%)  1
INTRA-ABDOMINAL HAEMORRHAGE  1  1/66 (1.52%)  1 0/18 (0.00%)  0
General disorders     
ADVERSE DRUG REACTION  1  2/66 (3.03%)  2 0/18 (0.00%)  0
DISEASE PROGRESSION  1  2/66 (3.03%)  2 1/18 (5.56%)  1
MALAISE  1  1/66 (1.52%)  1 0/18 (0.00%)  0
PYREXIA  1  1/66 (1.52%)  1 0/18 (0.00%)  0
Immune system disorders     
CYTOKINE RELEASE SYNDROME  1  1/66 (1.52%)  1 0/18 (0.00%)  0
Infections and infestations     
BILIARY TRACT INFECTION  1  1/66 (1.52%)  2 0/18 (0.00%)  0
CONJUNCTIVITIS  1  1/66 (1.52%)  1 0/18 (0.00%)  0
GASTRIC INFECTION  1  1/66 (1.52%)  1 0/18 (0.00%)  0
LOWER RESPIRATORY TRACT INFECTION  1  1/66 (1.52%)  1 0/18 (0.00%)  0
WOUND INFECTION  1  0/66 (0.00%)  0 1/18 (5.56%)  1
Injury, poisoning and procedural complications     
INFUSION RELATED REACTION  1  1/66 (1.52%)  1 0/18 (0.00%)  0
OVERDOSE  1  1/66 (1.52%)  1 0/18 (0.00%)  0
Investigations     
LABORATORY TEST ABNORMAL  1  1/66 (1.52%)  1 0/18 (0.00%)  0
LIVER FUNCTION TEST INCREASED  1  2/66 (3.03%)  3 0/18 (0.00%)  0
Metabolism and nutrition disorders     
DECREASED APPETITE  1  1/66 (1.52%)  1 0/18 (0.00%)  0
HYPOCALCAEMIA  1  1/66 (1.52%)  1 0/18 (0.00%)  0
HYPOPHOSPHATAEMIA  1  1/66 (1.52%)  1 0/18 (0.00%)  0
Musculoskeletal and connective tissue disorders     
BACK PAIN  1  2/66 (3.03%)  2 0/18 (0.00%)  0
BONE PAIN  1  1/66 (1.52%)  1 0/18 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
TUMOUR HAEMORRHAGE  1  1/66 (1.52%)  1 0/18 (0.00%)  0
Nervous system disorders     
APHASIA  1  1/66 (1.52%)  1 0/18 (0.00%)  0
SPINAL CORD COMPRESSION  1  1/66 (1.52%)  1 0/18 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
ACUTE RESPIRATORY DISTRESS SYNDROME  1  1/66 (1.52%)  1 0/18 (0.00%)  0
Skin and subcutaneous tissue disorders     
RASH  1  1/66 (1.52%)  2 0/18 (0.00%)  0
Vascular disorders     
HYPOTENSION  1  4/66 (6.06%)  5 1/18 (5.56%)  1
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
IMCgp100 Weekly Dosing Regimen IMCgp100 Daily Dosing Regimen
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   66/66 (100.00%)      18/18 (100.00%)    
Blood and lymphatic system disorders     
ANAEMIA  1  4/66 (6.06%)  4 5/18 (27.78%)  5
LEUKOCYTOSIS  1  3/66 (4.55%)  3 1/18 (5.56%)  1
LYMPHOPENIA  1  13/66 (19.70%)  13 1/18 (5.56%)  1
THROMBOCYTOPENIA  1  2/66 (3.03%)  2 4/18 (22.22%)  4
Cardiac disorders     
SINUS TACHYCARDIA  1  5/66 (7.58%)  5 1/18 (5.56%)  1
TACHYCARDIA  1  7/66 (10.61%)  7 4/18 (22.22%)  4
Eye disorders     
ERYTHEMA OF EYELID  1  0/66 (0.00%)  0 1/18 (5.56%)  1
EYE IRRITATION  1  0/66 (0.00%)  0 1/18 (5.56%)  1
EYE PAIN  1  2/66 (3.03%)  2 1/18 (5.56%)  1
EYELID OEDEMA  1  0/66 (0.00%)  0 1/18 (5.56%)  1
OCULAR HYPERAEMIA  1  2/66 (3.03%)  2 1/18 (5.56%)  1
PERIORBITAL OEDEMA  1  30/66 (45.45%)  30 11/18 (61.11%)  11
Gastrointestinal disorders     
ABDOMINAL PAIN  1  9/66 (13.64%)  9 2/18 (11.11%)  2
ABDOMINAL PAIN UPPER  1  5/66 (7.58%)  5 1/18 (5.56%)  1
CONSTIPATION  1  14/66 (21.21%)  14 3/18 (16.67%)  3
DIARRHOEA  1  10/66 (15.15%)  10 5/18 (27.78%)  5
DYSPEPSIA  1  4/66 (6.06%)  4 1/18 (5.56%)  1
NAUSEA  1  34/66 (51.52%)  34 10/18 (55.56%)  10
TOOTHACHE  1  0/66 (0.00%)  0 1/18 (5.56%)  1
VOMITING  1  24/66 (36.36%)  24 10/18 (55.56%)  10
General disorders     
ASTHENIA  1  1/66 (1.52%)  1 1/18 (5.56%)  1
AXILLARY PAIN  1  2/66 (3.03%)  2 1/18 (5.56%)  1
CHEST PAIN  1  7/66 (10.61%)  7 0/18 (0.00%)  0
CHILLS  1  17/66 (25.76%)  17 9/18 (50.00%)  9
FACE OEDEMA  1  13/66 (19.70%)  13 3/18 (16.67%)  3
FATIGUE  1  35/66 (53.03%)  35 10/18 (55.56%)  10
INFLUENZA LIKE ILLNESS  1  13/66 (19.70%)  13 5/18 (27.78%)  5
MALAISE  1  2/66 (3.03%)  2 1/18 (5.56%)  1
OEDEMA  1  4/66 (6.06%)  4 1/18 (5.56%)  1
OEDEMA PERIPHERAL  1  10/66 (15.15%)  10 8/18 (44.44%)  8
PAIN  1  2/66 (3.03%)  2 2/18 (11.11%)  2
PERIPHERAL SWELLING  1  6/66 (9.09%)  6 2/18 (11.11%)  2
PYREXIA  1  34/66 (51.52%)  34 13/18 (72.22%)  13
Immune system disorders     
HYPERSENSITIVITY  1  1/66 (1.52%)  1 1/18 (5.56%)  1
Infections and infestations     
ANGULAR CHEILITIS  1  4/66 (6.06%)  4 0/18 (0.00%)  0
CATHETER SITE INFECTION  1  0/66 (0.00%)  0 1/18 (5.56%)  1
CONJUNCTIVITIS  1  5/66 (7.58%)  5 0/18 (0.00%)  0
LOWER RESPIRATORY TRACT INFECTION  1  3/66 (4.55%)  3 2/18 (11.11%)  2
NASOPHARYNGITIS  1  2/66 (3.03%)  2 1/18 (5.56%)  1
PNEUMONIA  1  0/66 (0.00%)  0 1/18 (5.56%)  1
RASH PUSTULAR  1  0/66 (0.00%)  0 1/18 (5.56%)  1
RHINITIS  1  6/66 (9.09%)  6 0/18 (0.00%)  0
UPPER RESPIRATORY TRACT INFECTION  1  4/66 (6.06%)  4 1/18 (5.56%)  1
URINARY TRACT INFECTION  1  4/66 (6.06%)  4 1/18 (5.56%)  1
Injury, poisoning and procedural complications     
CONTUSION  1  2/66 (3.03%)  2 1/18 (5.56%)  1
Investigations     
BLOOD ALKALINE PHOSPHATASE INCREASED  1  3/66 (4.55%)  3 2/18 (11.11%)  2
BLOOD BILIRUBIN INCREASED  1  1/66 (1.52%)  1 1/18 (5.56%)  1
BLOOD CREATININE INCREASED  1  1/66 (1.52%)  1 1/18 (5.56%)  1
TRANSAMINASES INCREASED  1  1/66 (1.52%)  1 3/18 (16.67%)  3
WEIGHT DECREASED  1  1/66 (1.52%)  1 2/18 (11.11%)  2
Metabolism and nutrition disorders     
DECREASED APPETITE  1  9/66 (13.64%)  9 0/18 (0.00%)  0
DEHYDRATION  1  4/66 (6.06%)  4 0/18 (0.00%)  0
HYPERGLYCAEMIA  1  1/66 (1.52%)  1 1/18 (5.56%)  1
HYPOALBUMINAEMIA  1  3/66 (4.55%)  3 2/18 (11.11%)  2
HYPOCALCAEMIA  1  2/66 (3.03%)  2 1/18 (5.56%)  1
HYPOKALAEMIA  1  1/66 (1.52%)  1 1/18 (5.56%)  1
HYPOMAGNESAEMIA  1  2/66 (3.03%)  2 2/18 (11.11%)  2
HYPONATRAEMIA  1  2/66 (3.03%)  2 1/18 (5.56%)  1
HYPOPHOSPHATAEMIA  1  5/66 (7.58%)  5 3/18 (16.67%)  3
HYPOPROTEINAEMIA  1  0/66 (0.00%)  0 1/18 (5.56%)  1
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  7/66 (10.61%)  7 3/18 (16.67%)  3
BACK PAIN  1  14/66 (21.21%)  14 2/18 (11.11%)  2
GROIN PAIN  1  2/66 (3.03%)  2 1/18 (5.56%)  1
MUSCULOSKELETAL PAIN  1  3/66 (4.55%)  3 1/18 (5.56%)  1
MYALGIA  1  6/66 (9.09%)  6 1/18 (5.56%)  1
NECK PAIN  1  3/66 (4.55%)  3 2/18 (11.11%)  2
PAIN IN EXTREMITY  1  9/66 (13.64%)  9 1/18 (5.56%)  1
Nervous system disorders     
DIZZINESS  1  4/66 (6.06%)  4 0/18 (0.00%)  0
HEADACHE  1  16/66 (24.24%)  16 6/18 (33.33%)  6
LETHARGY  1  5/66 (7.58%)  5 0/18 (0.00%)  0
PARAESTHESIA  1  10/66 (15.15%)  10 1/18 (5.56%)  1
SPEECH DISORDER  1  0/66 (0.00%)  0 1/18 (5.56%)  1
SYNCOPE  1  0/66 (0.00%)  0 1/18 (5.56%)  1
Psychiatric disorders     
HALLUCINATION  1  0/66 (0.00%)  0 1/18 (5.56%)  1
INSOMNIA  1  4/66 (6.06%)  4 0/18 (0.00%)  0
Renal and urinary disorders     
HYDRONEPHROSIS  1  0/66 (0.00%)  0 1/18 (5.56%)  1
POLLAKIURIA  1  1/66 (1.52%)  1 1/18 (5.56%)  1
Respiratory, thoracic and mediastinal disorders     
COUGH  1  16/66 (24.24%)  16 2/18 (11.11%)  2
DYSPNOEA  1  6/66 (9.09%)  6 2/18 (11.11%)  2
HICCUPS  1  0/66 (0.00%)  0 1/18 (5.56%)  1
HYPOXIA  1  3/66 (4.55%)  3 1/18 (5.56%)  1
OROPHARYNGEAL PAIN  1  4/66 (6.06%)  4 1/18 (5.56%)  1
PRODUCTIVE COUGH  1  1/66 (1.52%)  1 1/18 (5.56%)  1
RALES  1  4/66 (6.06%)  4 0/18 (0.00%)  0
WHEEZING  1  2/66 (3.03%)  2 1/18 (5.56%)  1
Skin and subcutaneous tissue disorders     
BLISTER  1  2/66 (3.03%)  2 2/18 (11.11%)  2
BLOOD BLISTER  1  2/66 (3.03%)  2 1/18 (5.56%)  1
COLD SWEAT  1  1/66 (1.52%)  1 1/18 (5.56%)  1
DRY SKIN  1  18/66 (27.27%)  18 5/18 (27.78%)  5
ERYTHEMA  1  17/66 (25.76%)  17 2/18 (11.11%)  2
GENERALISED ERYTHEMA  1  0/66 (0.00%)  0 1/18 (5.56%)  1
HAIR COLOUR CHANGES  1  7/66 (10.61%)  7 1/18 (5.56%)  1
ONYCHOCLASIS  1  0/66 (0.00%)  0 1/18 (5.56%)  1
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME  1  2/66 (3.03%)  2 1/18 (5.56%)  1
PRURITUS  1  43/66 (65.15%)  43 16/18 (88.89%)  16
RASH  1  47/66 (71.21%)  47 10/18 (55.56%)  10
RASH ERYTHEMATOUS  1  9/66 (13.64%)  9 5/18 (27.78%)  5
RASH GENERALISED  1  1/66 (1.52%)  1 1/18 (5.56%)  1
RASH MACULO-PAPULAR  1  17/66 (25.76%)  17 6/18 (33.33%)  6
RASH PRURITIC  1  2/66 (3.03%)  2 1/18 (5.56%)  1
SKIN EXFOLIATION  1  19/66 (28.79%)  19 5/18 (27.78%)  5
VITILIGO  1  9/66 (13.64%)  9 1/18 (5.56%)  1
Vascular disorders     
FLUSHING  1  11/66 (16.67%)  11 1/18 (5.56%)  1
HAEMORRHAGE  1  0/66 (0.00%)  0 1/18 (5.56%)  1
HYPERTENSION  1  7/66 (10.61%)  7 1/18 (5.56%)  1
HYPOTENSION  1  20/66 (30.30%)  20 7/18 (38.89%)  7
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
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.
Publication/presentation (manuscript, abstract or poster) to a journal/scientific meeting is sent to sponsor for review at least 1 month before submission who may delay submission by up to 90 days if it reasonably believes that publication of results may compromise its intellectual property rights or else insist that such data are removed. No single center/groups of centers may publish individually. Publication will not include confidential information without the permission of the sponsor.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chris Holland, Executive Director Head of Biostatistics
Organization: Immunocore, LLC
Phone: 1-267-589-9204
EMail: chris.holland2@immunocore.com
Layout table for additonal information
Responsible Party: Immunocore Ltd
ClinicalTrials.gov Identifier: NCT01211262    
Other Study ID Numbers: IMCgp100/01
2010-019290-15 ( EudraCT Number )
First Submitted: September 28, 2010
First Posted: September 29, 2010
Results First Submitted: June 9, 2020
Results First Posted: July 8, 2020
Last Update Posted: July 8, 2020