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Trial record 53 of 721 for:    colon cancer AND 5-FU

Sym004 vs Standard of Care in Subjects With Metastatic Colorectal Cancer

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: NCT02083653
Recruitment Status : Completed
First Posted : March 11, 2014
Results First Posted : December 24, 2018
Last Update Posted : April 16, 2019
Sponsor:
Information provided by (Responsible Party):
Symphogen A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Colorectal Cancer
Interventions Drug: Sym004 (12 mg/kg)
Drug: Sym004 (9/6 mg/kg)
Other: Best Supportive Care (BSC)
Drug: Fluorouracil (5-FU)
Drug: Capecitabine
Enrollment 254
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Hide Arm/Group Description

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two monoclonal antibodies (mAbs) (futuximab and modotuximab) which bind to two non-overlapping epitopes of the epidermal growth factor receptor (EGFR).

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Period Title: Overall Study
Started 83 86 85
Completed 1 1 1
Not Completed 82 85 84
Reason Not Completed
Randomized but not Treated             0             2             7
Adverse Event             12             5             4
Lost to Follow-up             1             0             0
Death             2             2             2
Progressive Disease             65             73             63
Withdrawal by Subject             2             1             2
Other Events             0             2             2
Reason Missing             0             0             4
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice Total
Hide Arm/Group Description

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Total of all reporting groups
Overall Number of Baseline Participants 83 86 85 254
Hide Baseline Analysis Population Description
The baseline analysis population was the intent-to-treat (ITT) analysis set.
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 79 participants 86 participants 84 participants 249 participants
62.2  (9.91) 64.2  (10.41) 61.4  (10.70) 62.6  (10.38)
[1]
Measure Description: Age is relative to time of informed consent for this trial.
[2]
Measure Analysis Population Description: The age summary does not include subjects living in Germany.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants 86 participants 85 participants 254 participants
Female
31
  37.3%
32
  37.2%
31
  36.5%
94
  37.0%
Male
52
  62.7%
54
  62.8%
54
  63.5%
160
  63.0%
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants 86 participants 85 participants 254 participants
Hispanic or Latino
5
   6.0%
5
   5.8%
5
   5.9%
15
   5.9%
Not Hispanic or Latino
69
  83.1%
72
  83.7%
70
  82.4%
211
  83.1%
Unknown or Not Reported
9
  10.8%
9
  10.5%
10
  11.8%
28
  11.0%
[1]
Measure Description: Ethnicity is presented as 'Not Reported’ for subjects living in France.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants 86 participants 85 participants 254 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   1.2%
0
   0.0%
0
   0.0%
1
   0.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   1.2%
2
   2.3%
0
   0.0%
3
   1.2%
White
72
  86.7%
75
  87.2%
73
  85.9%
220
  86.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
9
  10.8%
9
  10.5%
12
  14.1%
30
  11.8%
[1]
Measure Description: Race is presented as ‘Not Reported’ for subjects living in France.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Austria Number Analyzed 83 participants 86 participants 85 participants 254 participants
0 1 1 2
Belgium Number Analyzed 83 participants 86 participants 85 participants 254 participants
3 6 5 14
Hungary Number Analyzed 83 participants 86 participants 85 participants 254 participants
0 1 5 6
United States Number Analyzed 83 participants 86 participants 85 participants 254 participants
8 6 8 22
Poland Number Analyzed 83 participants 86 participants 85 participants 254 participants
10 8 7 25
Italy Number Analyzed 83 participants 86 participants 85 participants 254 participants
17 12 20 49
France Number Analyzed 83 participants 86 participants 85 participants 254 participants
9 9 10 28
Germany Number Analyzed 83 participants 86 participants 85 participants 254 participants
4 0 1 5
Russia Number Analyzed 83 participants 86 participants 85 participants 254 participants
8 12 10 30
Spain Number Analyzed 83 participants 86 participants 85 participants 254 participants
24 31 18 73
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters (cm)
Number Analyzed 83 participants 86 participants 85 participants 254 participants
168.9  (10.82) 169.1  (9.71) 167.9  (9.56) 168.7  (10.01)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 83 participants 86 participants 85 participants 254 participants
75.3  (13.51) 74.0  (14.14) 76.0  (16.13) 75.1  (14.61)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 83 participants 86 participants 85 participants 254 participants
26.5  (4.43) 25.8  (4.26) 26.8  (4.59) 26.4  (4.43)
1.Primary Outcome
Title Overall Survival (OS) Time
Hide Description

OS based on product-limit (Kaplan-Meier) estimates. Confidence intervals for the median are calculated according to Brookmeyer and Crowley.

If a subject had not died, survival time was censored at the last date the subject was known to be alive.

Time Frame From randomization until the date of death (assessed up to 32 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the intent-to-treat (ITT) subpopulation, which includes all subjects who were randomized to investigational medicinal product (IMP). Analyses performed on the ITT analysis set will take into account subjects’ allocation to treatment groups as randomized and not as treated.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Overall Number of Participants Analyzed 83 86 85
Median (95% Confidence Interval)
Unit of Measure: months
7.9
(6.5 to 9.9)
10.3
(9.0 to 12.9)
9.6
(8.3 to 12.2)
2.Secondary Outcome
Title Best Overall Response (OR) According to the Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
Hide Description Tumor assessments were done via computed tomography (CT) or magnetic resonance imaging (MRI) scans and evaluated per RECIST v1.1. The assessment for measurable disease during screening (within 14 days prior to Day 1) acts as the baseline assessment. Best OR was summarized for each treatment group by means of counts and percentages for the following categories: Complete Response (CR: disappearance of all target lesions), Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions), Progressive Disease (PD: at least a 20% increase in the sum of diameters of target lesions), Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) or Not Evaluable (NE).
Time Frame From randomization until first radiological confirmed or clinical progression event, or death due to any cause, within 12 weeks after last tumor assessment (assessed up to 32 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the ITT subpopulation, which includes all subjects who were randomized to IMP. Analyses performed on the ITT analysis set will take into account subjects’ allocation to treatment groups as randomized and not as treated.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Overall Number of Participants Analyzed 83 86 85
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response (CR)
0
   0.0%
0
   0.0%
1
   1.2%
Partial Response (PR)
11
  13.3%
8
   9.3%
1
   1.2%
Stable Disease (SD)
40
  48.2%
47
  54.7%
37
  43.5%
Progressive Disease (PD)
27
  32.5%
28
  32.6%
31
  36.5%
Not Evaluable (NE)
5
   6.0%
3
   3.5%
15
  17.6%
3.Secondary Outcome
Title Progression Free Survival (PFS) Time
Hide Description PFS based on product-limit (Kaplan-Meier) estimates. Confidence intervals for the median are calculated according to Brookmeyer and Crowley. Death will only be considered as an event if it occurs within 12 weeks after last tumor response assessment without progression.
Time Frame From randomization until first event, where an event can be a progression (radiological confirmed or clinical progression) or death due to any cause (assessed up to 32 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the ITT subpopulation, which includes all subjects who were randomized to IMP. Analyses performed on the ITT analysis set will take into account subjects’ allocation to treatment groups as randomized and not as treated.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Overall Number of Participants Analyzed 83 86 85
Median (95% Confidence Interval)
Unit of Measure: months
2.8
(1.8 to 3.2)
2.7
(2.6 to 3.3)
2.6
(1.4 to 3.1)
4.Secondary Outcome
Title Time to Treatment Failure (TTF)
Hide Description TTF based on product-limit (Kaplan-Meier) estimates. Confidence intervals for the median are calculated according to Brookmeyer and Crowley.
Time Frame From randomization until treatment discontinuation for any reason, including disease progression or death (assessed up to 32 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the ITT subpopulation, which includes all subjects who were randomized to IMP. Analyses performed on the ITT analysis set will take into account subjects' allocation to treatment groups as randomized and not as treated. Subjects who were randomized but not treated have been censored at the date of randomization.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Overall Number of Participants Analyzed 83 86 85
Median (95% Confidence Interval)
Unit of Measure: months
2.1
(1.4 to 2.7)
2.6
(2.2 to 2.6)
1.6
(1.2 to 2.7)
5.Secondary Outcome
Title Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03).
Hide Description AEs were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. The incidence and type of AEs (i.e., serious AE [SAE], treatment-emergent AE [TEAE]) were summarized by dose cohort according to MedDRA system organ classes and preferred terms. An AE was considered as treatment-emergent if it occurred during or after the first IMP administration. An AE that occurred before the first IMP administration and worsened thereafter was also considered an AE. Worsening was reported as a new AE.
Time Frame From Baseline up to 28 days after the last IMP administration.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the safety analysis subpopulation, which includes all subjects who were administered any dose of IMP, and in addition those subjects in Arm C for which the intended control treatment is BSC. Subjects will be analyzed as treated and not as randomized.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Overall Number of Participants Analyzed 83 84 78
Measure Type: Count of Participants
Unit of Measure: Participants
At least one TEAE
83
 100.0%
84
 100.0%
67
  85.9%
At least one Serious TEAE
27
  32.5%
23
  27.4%
12
  15.4%
TEAE leading to dose reduction
29
  34.9%
17
  20.2%
8
  10.3%
TEAE leading to interruption of trial treatment
58
  69.9%
47
  56.0%
10
  12.8%
TEAE leading to trial treatment withdrawal
12
  14.5%
5
   6.0%
6
   7.7%
TEAE related to trial treatment
81
  97.6%
80
  95.2%
46
  59.0%
TEAE, Grade >=3
67
  80.7%
53
  63.1%
25
  32.1%
Dermatologic toxicity
78
  94.0%
78
  92.9%
8
  10.3%
Infusion-related reaction
27
  32.5%
26
  31.0%
0
   0.0%
TEAE resulting in death
4
   4.8%
4
   4.8%
3
   3.8%
Related Serious TEAE
9
  10.8%
6
   7.1%
2
   2.6%
Related TEAE leading to dose reduction
29
  34.9%
17
  20.2%
6
   7.7%
Related TEAE leading to interruption of treatment
53
  63.9%
42
  50.0%
7
   9.0%
Related TEAE leading to treatment withdrawal
9
  10.8%
2
   2.4%
3
   3.8%
Related TEAE, Grade >=3
58
  69.9%
41
  48.8%
9
  11.5%
Related TEAE resulting in death
0
   0.0%
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Relative Dose Intensity of Sym004
Hide Description

Treatment duration (weeks) is calculated as [(last dose date of Sym004 - first dose date of Sym004)+7] / 7 days.

Sym004 dose received (mg/kg) is calculated as (total dose administered (mg)/weight (kg)).

Dose Intensity is calculated as (cumulative Sym004 dose (mg/kg) / treatment duration (weeks)).

Relative Dose Intensity is calculated as (dose intensity / planned dose intensity at randomization)*100.

Percentages are based on the number of subjects in the safety analysis set.

Time Frame From first dose of study drug until disease progression (assessed up to 32 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the safety analysis subpopulation, which includes all subjects who were administered any dose of IMP. Subjects will be analyzed as treated and not as randomized.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg)
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Overall Number of Participants Analyzed 83 84
Mean (Standard Deviation)
Unit of Measure: percentage of relative dose intensity
80.49  (20.020) 88.91  (13.843)
7.Secondary Outcome
Title Pharmacokinetic (PK) Parameters: Sym004 Concentrations
Hide Description

The Sym004 serum concentration used for the PK evaluation was calculated as the sum of the serum concentrations of the 2 component monoclonal antibodies of Sym004 (futuximab and modotuximab).

Trough Concentration (Ctrough) is equivalent to the concentration collected at the pre-dose timepoint.

Maximum Concentration (Cmax) is equivalent to the concentration collected at the end of infusion (EOI) timepoint.

Time Frame Weeks 3, 5, and 7 and at the End of Treatment visit, including a Week 1 and Week 2 subset.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the PK analysis set. Bioanalysis for serum concentration was done for a subset of subjects (N=19) at all scheduled timepoints; it was carried out only at Weeks 3, 5, 7 and the End of Treatment visit for all other subjects. Additionally, the Week 1 Day 1 EOI concentration for Subject 2740012 was assessed.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg)
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Overall Number of Participants Analyzed 80 83
Mean (Standard Deviation)
Unit of Measure: ug/mL
Screening (Pre-dose) Number Analyzed 11 participants 8 participants
0.50  (0.000) 0.50  (0.000)
Week 1 Day 1 (Pre-dose) Number Analyzed 11 participants 8 participants
0.50  (0.000) 0.75  (0.700)
Week 1 Day 1 (EOI) Number Analyzed 12 participants 8 participants
182.95  (97.686) 174.44  (47.023)
Week 1 Day 1 (0.5 hours after EOI) Number Analyzed 11 participants 8 participants
214.98  (46.242) 184.84  (33.103)
Week 1 Day 1 (1 hour after EOI) Number Analyzed 11 participants 8 participants
209.80  (60.707) 189.24  (38.923)
Week 1 Day 1 (2 hours after EOI) Number Analyzed 11 participants 8 participants
197.31  (65.801) 181.68  (37.577)
Week 1 Day 1 (4 hours after EOI) Number Analyzed 11 participants 8 participants
188.75  (68.421) 171.63  (35.862)
Week 2 Day 1 (Pre-dose) Number Analyzed 11 participants 8 participants
45.37  (28.604) 38.76  (10.311)
Week 2 Day 1 (EOI) Number Analyzed 11 participants 8 participants
275.42  (80.975) 145.91  (47.950)
Week 3 Day 1 (Pre-dose) Number Analyzed 76 participants 80 participants
92.66  (38.443) 44.26  (20.995)
Week 3 Day 1 (EOI) Number Analyzed 73 participants 79 participants
323.35  (83.412) 170.18  (50.323)
Week 5 Day 1 (Pre-dose) Number Analyzed 58 participants 63 participants
125.73  (61.644) 49.26  (30.252)
Week 5 Day 1 (EOI) Number Analyzed 56 participants 63 participants
354.91  (108.263) 168.94  (67.901)
Week 7 Day 1 (Pre-dose) Number Analyzed 41 participants 55 participants
128.30  (77.437) 58.38  (47.505)
Week 7 Day 1 (EOI) Number Analyzed 37 participants 53 participants
346.83  (136.083) 163.11  (74.967)
End of Treatment Number Analyzed 57 participants 55 participants
64.55  (79.250) 17.61  (24.474)
8.Secondary Outcome
Title Pharmacokinetic (PK) Parameters: Time of Maximum Plasma Concentration (Tmax)
Hide Description Tmax was defined as the time the PK sample was taken at end of infusion (EOI) relative to the start time of infusion (i.e., time between the start of infusion and the time of the EOI sample). For presentation of individual PK parameters and calculation of mean parameters, half of the lower limit of quantitation (LLOQ) value was used for concentration values below the LLOQ. The Sym004 serum concentration used for the PK evaluation was calculated as the sum of the serum concentrations of the 2 component monoclonal antibodies of Sym004, futuximab and modotuximab.
Time Frame Day 1 on Weeks 1-3 followed by Week 5 Day 1 and Week 7 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the PK analysis set, defined as subjects having at least 1 Sym004 serum concentration above the LLOQ. Exposure to Sym004 was confirmed in the majority of subjects treated with Sym004 for at least 1 timepoint post-dose.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg)
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Overall Number of Participants Analyzed 80 83
Mean (Standard Deviation)
Unit of Measure: hours
Week 1 Day 1 Number Analyzed 12 participants 8 participants
3.14  (0.822) 2.79  (0.210)
Week 2 Day 1 Number Analyzed 11 participants 8 participants
2.82  (0.306) 2.33  (0.459)
Week 3 Day 1 Number Analyzed 72 participants 79 participants
3.01  (0.555) 2.34  (0.477)
Week 5 Day 1 Number Analyzed 56 participants 63 participants
2.74  (0.532) 2.06  (0.448)
Week 7 Day 1 Number Analyzed 37 participants 52 participants
2.83  (0.867) 2.06  (0.473)
9.Secondary Outcome
Title Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time
Hide Description A validated double antigen bridging ELISA was used for screening, confirmation, and titration of patient samples for anti-Sym004 ADA. Using rabbit anti-Sym004 as an ADA control antibody, the lower limit of detection was 54 ng/mL in the absence of Sym004 and 500 ng/mL in the presence of Sym004 at 5 µg/mL The timepoints for ADA sampling were chosen by the original sponsor for this trial. After the trial was transferred to Symphogen A/S, it was determined that not all samples were necessary for analysis. This is why the collection time points specified in the Outcome Measure Time Frame do not match with the Outcome Measure Data Table.
Time Frame Every two weeks (Days 15, 29, and 43) followed by every six weeks thereafter (Days 78, 120, 162, etc.) until the End of Treatment Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the safety analysis subpopulation, which includes all subjects who were administered any dose of IMP. Subjects will be analyzed as treated and not as randomized.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg)
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Overall Number of Participants Analyzed 83 84
Measure Type: Count of Participants
Unit of Measure: Participants
Screening Negative
78
  94.0%
81
  96.4%
Positive
2
   2.4%
0
   0.0%
Not Reportable
1
   1.2%
0
   0.0%
Missing
2
   2.4%
3
   3.6%
Week 5 Day 1 Negative
59
  71.1%
62
  73.8%
Positive
0
   0.0%
0
   0.0%
Not Reportable
0
   0.0%
0
   0.0%
Missing
24
  28.9%
22
  26.2%
Week 12 Negative
24
  28.9%
35
  41.7%
Positive
0
   0.0%
0
   0.0%
Not Reportable
0
   0.0%
0
   0.0%
Missing
59
  71.1%
49
  58.3%
Week 13 Negative
1
   1.2%
1
   1.2%
Positive
0
   0.0%
0
   0.0%
Not Reportable
0
   0.0%
0
   0.0%
Missing
82
  98.8%
83
  98.8%
Week 24 Negative
0
   0.0%
1
   1.2%
Positive
0
   0.0%
0
   0.0%
Not Reportable
0
   0.0%
0
   0.0%
Missing
83
 100.0%
83
  98.8%
End of Treatment Visit Negative
60
  72.3%
55
  65.5%
Positive
0
   0.0%
0
   0.0%
Not Reportable
0
   0.0%
0
   0.0%
Missing
23
  27.7%
29
  34.5%
10.Secondary Outcome
Title Quality of Life Assessed by the EORTC QLQ-C30 (Version 3)
Hide Description

Scale: European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (Version 3) [QLQ-C30, Version 3].

The QLQ-C30 is a 30-question scale used to assess cancer patients' quality of life based on 15 factors (e.g., global health status, physical functioning, role functioning, etc.). The scale is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100:

  • A high score for a functional scale represents a healthy level of functioning.
  • A high score for the global health status represents a high quality of life.
  • A high score for a symptom scale/item represents a high level of symptomatology (problems).
Time Frame Assessed every 6 weeks (week 1 and week 7 reported)
Hide Outcome Measure Data
Hide Analysis Population Description
This measure was self-reported. Numbers analyzed between Week 1 and Week 7 differ from each other, as well from the overall number of subjects analyzed. Data could not be collected from subjects not compliant with reporting or once discontinued.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Overall Number of Participants Analyzed 83 86 85
Mean (Full Range)
Unit of Measure: score on a scale
Global Health Status (Week 1 Day 1) Number Analyzed 74 participants 79 participants 66 participants
55.5
(0 to 92)
59.7
(8 to 100)
55.8
(8 to 100)
Global Health Status (Week 7 Day 1) Number Analyzed 48 participants 48 participants 36 participants
57.4
(25 to 100)
59.4
(17 to 100)
59.7
(17 to 100)
Physical Functioning (Week 1 Day 1) Number Analyzed 75 participants 81 participants 69 participants
76.4
(7 to 100)
78.7
(27 to 100)
77.7
(27 to 100)
Physical Functioning (Week 7 Day 1) Number Analyzed 51 participants 49 participants 36 participants
82.1
(13 to 100)
83.0
(47 to 100)
76.7
(40 to 100)
Role Functioning (Week 1 Day 1) Number Analyzed 76 participants 81 participants 69 participants
75.0
(0 to 100)
76.4
(0 to 100)
72.5
(0 to 100)
Role Functioning (Week 7 Day 1) Number Analyzed 51 participants 49 participants 36 participants
81.1
(33 to 100)
82.4
(50 to 100)
72.8
(17 to 100)
Emotional Functioning (Week 1 Day 1) Number Analyzed 73 participants 79 participants 67 participants
76.6
(17 to 100)
77.8
(17 to 100)
73.2
(0 to 100)
Emotional Functioning (Week 7 Day 1) Number Analyzed 49 participants 48 participants 36 participants
74.8
(0 to 100)
82.7
(33 to 100)
75.3
(17 to 100)
Cognitive Functioning (Week 1 Day 1) Number Analyzed 74 participants 79 participants 67 participants
87.4
(33 to 100)
86.2
(17 to 100)
87.5
(50 to 100)
Cognitive Functioning (Week 7 Day 1) Number Analyzed 49 participants 48 participants 36 participants
88.1
(33 to 100)
88.5
(33 to 100)
87.0
(33 to 100)
Social Functioning (Week 1 Day 1) Number Analyzed 74 participants 79 participants 67 participants
78.2
(17 to 100)
80.2
(17 to 100)
75.4
(17 to 100)
Social Functioning (Week 7 Day 1) Number Analyzed 49 participants 48 participants 36 participants
77.9
(0 to 100)
83.4
(50 to 100)
72.7
(0 to 100)
Fatigue Symptoms (Week 1 Day 1) Number Analyzed 75 participants 81 participants 69 participants
35.3
(0 to 89)
32.2
(0 to 100)
34.7
(0 to 100)
Fatigue Symptoms (Week 7 Day 1) Number Analyzed 51 participants 49 participants 36 participants
26.3
(0 to 78)
25.3
(0 to 78)
33.2
(0 to 78)
Nausea & Vomiting Symptoms (Week 1 Day 1) Number Analyzed 76 participants 81 participants 69 participants
7.9
(0 to 67)
6.4
(0 to 100)
7.8
(0 to 83)
Nausea & Vomiting Symptoms (Week 7 Day 1) Number Analyzed 51 participants 49 participants 36 participants
5.6
(0 to 33)
5.1
(0 to 50)
8.4
(0 to 50)
Pain Symptoms (Week 1 Day 1) Number Analyzed 76 participants 81 participants 69 participants
27.2
(0 to 100)
23.6
(0 to 100)
27.8
(0 to 100)
Pain Symptoms (Week 7 Day 1) Number Analyzed 50 participants 49 participants 36 participants
12.7
(0 to 50)
14.6
(0 to 67)
24.1
(0 to 83)
Dyspnoea Symptoms (Week 1 Day 1) Number Analyzed 75 participants 81 participants 69 participants
15.9
(0 to 100)
17.2
(0 to 100)
16.4
(0 to 100)
Dyspnoea Symptoms (Week 7 Day 1) Number Analyzed 51 participants 49 participants 36 participants
10.4
(0 to 67)
8.8
(0 to 100)
15.7
(0 to 100)
Insomnia Symptoms (Week 1 Day 1) Number Analyzed 76 participants 80 participants 69 participants
29.3
(0 to 100)
19.1
(0 to 100)
21.7
(0 to 100)
Insomnia Symptoms (Week 7 Day 1) Number Analyzed 51 participants 49 participants 36 participants
27.4
(0 to 100)
16.9
(0 to 100)
16.6
(0 to 67)
Appetite Loss Symptoms (Week 1 Day 1) Number Analyzed 76 participants 81 participants 69 participants
22.3
(0 to 100)
17.6
(0 to 100)
22.2
(0 to 100)
Appetite Loss Symptoms (Week 7 Day 1) Number Analyzed 51 participants 49 participants 36 participants
16.9
(0 to 100)
17.5
(0 to 67)
23.0
(0 to 100)
Constipation Symptoms (Week 1 Day 1) Number Analyzed 73 participants 79 participants 67 participants
15.0
(0 to 67)
16.0
(0 to 100)
11.4
(0 to 100)
Constipation Symptoms (Week 7 Day 1) Number Analyzed 49 participants 48 participants 36 participants
11.5
(0 to 67)
8.3
(0 to 67)
11.1
(0 to 67)
Diarrhoea Symptoms (Week 1 Day 1) Number Analyzed 74 participants 78 participants 67 participants
12.5
(0 to 100)
8.5
(0 to 100)
15.9
(0 to 100)
Diarrhoea Symptoms (Week 7 Day 1) Number Analyzed 49 participants 48 participants 36 participants
8.8
(0 to 100)
11.1
(0 to 67)
11.0
(0 to 67)
Financial Difficulties (Week 1 Day 1) Number Analyzed 74 participants 78 participants 67 participants
19.7
(0 to 67)
16.6
(0 to 100)
23.3
(0 to 100)
Financial Difficulties (Week 7 Day 1) Number Analyzed 48 participants 48 participants 36 participants
19.4
(0 to 100)
15.2
(0 to 67)
19.3
(0 to 100)
11.Secondary Outcome
Title Quality of Life Assessed by EORTC QLQ-CR29
Hide Description

Scale: European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Colorectal Cancer Module (QLQ-CR29).

The QLQ-CR29 is a 29-question scale used to assess colorectal cancer patients' quality of life based on 22 factors (e.g., body image, anxiety, weight, etc.). The scale is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100:

  • A high score for a functional scale/item represents an unhealthy level of functioning, with the exception of one (1) scale pertaining to sexual interest (separated by sex).
  • A high score for a symptom scale/item represents a high level of symptomatology (problems).
Time Frame Assessed every 6 weeks (week 1 and week 7 reported)
Hide Outcome Measure Data
Hide Analysis Population Description
This measure was self-reported. Numbers analyzed between Week 1 and Week 7 differ from each other, as well from the overall number of subjects analyzed. Data could not be collected from subjects not compliant with reporting or once discontinued.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Overall Number of Participants Analyzed 83 86 85
Mean (Full Range)
Unit of Measure: score on a scale
Body Image (Week 1 Day 1) Number Analyzed 74 participants 80 participants 69 participants
76.2
(0 to 100)
80.1
(0 to 100)
75.8
(0 to 100)
Body Image (Week 7 Day 1) Number Analyzed 52 participants 47 participants 36 participants
76.4
(11 to 100)
77.6
(33 to 100)
78.2
(0 to 100)
Anxiety (Week 1 Day 1) Number Analyzed 74 participants 81 participants 69 participants
50.0
(0 to 100)
48.2
(0 to 100)
43.0
(0 to 100)
Anxiety (Week 7 Day 1) Number Analyzed 52 participants 48 participants 36 participants
57.1
(0 to 100)
61.1
(0 to 100)
50.9
(0 to 100)
Weight (Week 1 Day 1) Number Analyzed 73 participants 81 participants 69 participants
79.5
(0 to 100)
85.6
(0 to 100)
78.3
(0 to 100)
Weight (Week 7 Day 1) Number Analyzed 52 participants 48 participants 36 participants
86.6
(33 to 100)
89.6
(33 to 100)
88.0
(0 to 100)
Sexual Function (Men) (Week 1 Day 1) Number Analyzed 45 participants 47 participants 41 participants
31.7
(0 to 100)
21.2
(0 to 100)
23.5
(0 to 100)
Sexual Function (Men) (Week 7 Day 1) Number Analyzed 30 participants 25 participants 21 participants
33.2
(0 to 100)
26.6
(0 to 67)
34.9
(0 to 100)
Sexual Function (Women) (Week 1 Day 1) Number Analyzed 24 participants 27 participants 23 participants
16.5
(0 to 33)
12.3
(0 to 67)
10.1
(0 to 67)
Sexual Function (Women) (Week 7 Day 1) Number Analyzed 16 participants 17 participants 15 participants
16.6
(0 to 67)
13.6
(0 to 67)
11.0
(0 to 33)
Urinary Frequency (Week 1 Day 1) Number Analyzed 75 participants 80 participants 68 participants
34.4
(0 to 100)
30.3
(0 to 83)
32.6
(0 to 100)
Urinary Frequency (Week 7 Day 1) Number Analyzed 52 participants 48 participants 35 participants
28.2
(0 to 100)
28.8
(0 to 67)
18.5
(0 to 67)
Blood and Mucus (Week 1 Day 1) Number Analyzed 74 participants 81 participants 67 participants
4.1
(0 to 50)
1.5
(0 to 33)
2.0
(0 to 33)
Blood and Mucus (Week 7 Day 1) Number Analyzed 52 participants 49 participants 36 participants
2.6
(0 to 33)
3.1
(0 to 67)
2.3
(0 to 33)
Stool Frequency (Week 1 Day 1) Number Analyzed 55 participants 68 participants 57 participants
15.5
(0 to 100)
11.3
(0 to 100)
14.1
(0 to 83)
Stool Frequency (Week 7 Day 1) Number Analyzed 40 participants 41 participants 32 participants
13.4
(0 to 50)
11.8
(0 to 83)
13.1
(0 to 67)
Urinary Incontinence (Week 1 Day 1) Number Analyzed 73 participants 79 participants 67 participants
8.2
(0 to 100)
7.5
(0 to 100)
7.4
(0 to 100)
Urinary Incontinence (Week 7 Day 1) Number Analyzed 52 participants 48 participants 35 participants
7.0
(0 to 67)
4.8
(0 to 67)
1.9
(0 to 33)
Dysuria (Week 1 Day 1) Number Analyzed 75 participants 80 participants 66 participants
4.0
(0 to 33)
2.9
(0 to 67)
3.0
(0 to 67)
Dysuria (Week 7 Day 1) Number Analyzed 51 participants 48 participants 35 participants
3.2
(0 to 33)
2.1
(0 to 33)
0.9
(0 to 33)
Abdominal Pain (Week 1 Day 1) Number Analyzed 74 participants 80 participants 68 participants
18.8
(0 to 100)
12.8
(0 to 100)
23.0
(0 to 100)
Abdominal Pain (Week 7 Day 1) Number Analyzed 51 participants 49 participants 36 participants
10.4
(0 to 67)
10.8
(0 to 67)
16.6
(0 to 67)
Buttock Pain (Week 1 Day 1) Number Analyzed 74 participants 80 participants 67 participants
11.6
(0 to 100)
10.8
(0 to 100)
9.9
(0 to 100)
Buttock Pain (Week 7 Day 1) Number Analyzed 52 participants 49 participants 36 participants
4.4
(0 to 33)
8.8
(0 to 67)
7.4
(0 to 67)
Bloated Feeling (Week 1 Day 1) Number Analyzed 73 participants 81 participants 69 participants
20.4
(0 to 100)
14.8
(0 to 67)
21.7
(0 to 100)
Bloated Feeling (Week 7 Day 1) Number Analyzed 52 participants 49 participants 36 participants
13.3
(0 to 67)
12.1
(0 to 33)
12.9
(0 to 67)
Dry Mouth (Weel 1 Day 1) Number Analyzed 74 participants 80 participants 69 participants
25.1
(0 to 100)
17.0
(0 to 67)
22.1
(0 to 100)
Dry Mouth (Weel 7 Day 1) Number Analyzed 52 participants 49 participants 36 participants
26.8
(0 to 100)
29.2
(0 to 100)
13.8
(0 to 67)
Hair Loss (Week 1 Day 1) Number Analyzed 72 participants 81 participants 66 participants
17.1
(0 to 100)
11.1
(0 to 100)
14.6
(0 to 100)
Hair Loss (Week 7 Day 1) Number Analyzed 52 participants 48 participants 36 participants
7.0
(0 to 100)
7.6
(0 to 67)
4.6
(0 to 100)
Trouble with Taste (Week 1 Day 1) Number Analyzed 73 participants 81 participants 66 participants
20.0
(0 to 100)
13.9
(0 to 100)
15.1
(0 to 100)
Trouble with Taste (Week 7 Day 1) Number Analyzed 52 participants 48 participants 36 participants
18.5
(0 to 100)
15.2
(0 to 67)
12.9
(0 to 100)
Flatulence (Week 1 Day 1) Number Analyzed 56 participants 68 participants 56 participants
18.3
(0 to 100)
19.5
(0 to 100)
23.1
(0 to 100)
Flatulence (Week 7 Day 1) Number Analyzed 40 participants 41 participants 32 participants
12.4
(0 to 67)
16.1
(0 to 67)
12.4
(0 to 33)
Faecal Incontinence (Week 1 Day 1) Number Analyzed 56 participants 68 participants 56 participants
8.9
(0 to 100)
8.8
(0 to 100)
7.1
(0 to 67)
Faecal Incontinence (Week 7 Day 1) Number Analyzed 40 participants 41 participants 32 participants
2.5
(0 to 33)
7.3
(0 to 67)
3.1
(0 to 33)
Sore Skin (Week 1 Day 1) Number Analyzed 55 participants 68 participants 55 participants
9.6
(0 to 67)
8.8
(0 to 67)
6.0
(0 to 33)
Sore Skin (Week 7 Day 1) Number Analyzed 40 participants 41 participants 32 participants
11.6
(0 to 33)
9.7
(0 to 67)
4.2
(0 to 67)
Embarrassed by Bowel Movement (Week 1 Day 1) Number Analyzed 55 participants 68 participants 55 participants
8.5
(0 to 100)
7.8
(0 to 100)
13.9
(0 to 100)
Embarrassed by Bowel Movement (Week 7 Day 1) Number Analyzed 40 participants 41 participants 32 participants
7.5
(0 to 67)
8.1
(0 to 67)
10.4
(0 to 67)
Stoma Care Problem (Week 1 Day 1) Number Analyzed 16 participants 20 participants 25 participants
16.6
(0 to 100)
3.3
(0 to 33)
6.6
(0 to 67)
Stoma Care Problem (Week 7 Day 1) Number Analyzed 10 participants 14 participants 8 participants
9.9
(0 to 33)
2.4
(0 to 33)
8.3
(0 to 33)
Impotence (Week 1 Day 1) Number Analyzed 44 participants 43 participants 41 participants
46.9
(0 to 100)
38.7
(0 to 100)
49.5
(0 to 100)
Impotence (Week 7 Day 1) Number Analyzed 28 participants 25 participants 21 participants
40.4
(0 to 100)
42.7
(0 to 100)
50.7
(0 to 100)
Dyspareunia (Week 1 Day 1) Number Analyzed 22 participants 23 participants 21 participants
12.1
(0 to 100)
7.2
(0 to 33)
11.0
(0 to 100)
Dyspareunia (Week 7 Day 1) Number Analyzed 14 participants 16 participants 15 participants
14.3
(0 to 67)
10.3
(0 to 33)
13.3
(0 to 67)
12.Secondary Outcome
Title Quality of Life Assessed by FACT-EGFRI-18 for Skin Rash
Hide Description

Scale: Functional Assessment of Cancer Therapy-Epidermal Growth Factor Receptor Inhibitor 18 (FACT-EGFRI-18).

The FACT-EGFRI-18 is an 18-question scale used to assess EGFR-inhibitor-treated cancer patients' quality of life relative to their experience of skin rash based on three (3) multi-item subscales. The subscales combined (i.e., Symptom Index) range in score from 0 to 72. A higher score represents a high level of symptomatology (problems).

High scores for all subscales represent a worse outcome:

  • The Physical subscale ranges in score from 0 to 28.
  • The Social/Emotional subscale ranges in score from 0 to 24.
  • The Functional subscale ranges in score from 0 to 20.
Time Frame Assessed every 3 weeks (week 1 and week 4 reported)
Hide Outcome Measure Data
Hide Analysis Population Description
This measure was self-reported. Numbers analyzed between Week 1 and Week 4 differ from each other, as well from the overall number of subjects analyzed. Data could not be collected from subjects not compliant with reporting or once discontinued.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Overall Number of Participants Analyzed 83 86 85
Mean (Full Range)
Unit of Measure: score on a scale
Physical (Week 1 Day 1) Number Analyzed 70 participants 78 participants 68 participants
22.9
(2 to 28)
23.1
(4 to 28)
24.3
(6 to 28)
Physical (Week 4 Day 1) Number Analyzed 68 participants 70 participants 58 participants
18.0
(4 to 28)
19.7
(5 to 28)
25.1
(16 to 28)
Social/Emotional (Week 1 Day 1) Number Analyzed 70 participants 78 participants 68 participants
21.5
(9 to 24)
21.5
(6 to 24)
22.6
(9 to 24)
Social/Emotional (Week 4 Day 1) Number Analyzed 68 participants 70 participants 58 participants
19.9
(7 to 24)
20.3
(5 to 24)
23.2
(15 to 24)
Functional (Week 1 Day 1) Number Analyzed 70 participants 78 participants 68 participants
17.9
(5 to 20)
18.3
(7 to 20)
18.7
(4 to 20)
Functional (Week 4 Day 1) Number Analyzed 68 participants 70 participants 58 participants
16.3
(3 to 20)
17.0
(6 to 20)
19.3
(13 to 20)
Symptom Index (Week 1 Day 1) Number Analyzed 70 participants 78 participants 68 participants
62.3
(18 to 72)
62.9
(20 to 72)
65.6
(19 to 72)
Symptom Index (Week 4 Day 1) Number Analyzed 68 participants 70 participants 58 participants
54.2
(16 to 72)
57.0
(22 to 72)
67.6
(46 to 72)
13.Post-Hoc Outcome
Title Overall Survival (OS) Time for Patients in Europe + United States With Double-Negative mCRC (EU+US DNmCRC)
Hide Description

OS based on product-limit (Kaplan-Meier) estimates. Confidence intervals for the median are calculated according to Brookmeyer and Crowley.

This outcome measure is considered exploratory. Because of the unanticipated long OS in the control group, initial exploratory subgroup analyses identified that findings in patients enrolled in Russia differed when compared with patients enrolled in the ITT subpopulation and the EU+US subpopulation. For this reason, subjects in Russia were excluded from further exploratory subset analyses that evaluated the effects of genomic parameters known to impact patient responses to anti-EGFR monoclonal antibodies. Removal of the outlier Russian subpopulation of patients provided a patient population that was more homogeneous with respect to their prior treatment regimens, thereby facilitating further exploratory analyses. If a subject had not died, survival time was censored at the last date the subject was known to be alive.

Time Frame From randomization until the date of death (assessed up to 32 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the EU+US DNmCRC analysis set, which is a genomically-defined subpopulation excluding patients with high frequency clonal RAS mutations and BRAF V600E mutations.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Overall Number of Participants Analyzed 62 57 51
Median (95% Confidence Interval)
Unit of Measure: months
8.9
(6.2 to 12.4)
11.9
(9.7 to 13.8)
8.4
(6.4 to 10.0)
14.Post-Hoc Outcome
Title Overall Survival (OS) Time for Patients in Europe + United States With Triple-Negative mCRC (EU+US TNmCRC)
Hide Description

OS based on product-limit (Kaplan-Meier) estimates. Confidence intervals for the median are calculated according to Brookmeyer and Crowley.

This outcome measure is considered exploratory. Because of the unanticipated long OS in the control group, initial exploratory subgroup analyses identified that findings in patients enrolled in Russia differed when compared with patients enrolled in the ITT subpopulation and the EU+US subpopulation. For this reason, subjects in Russia were excluded from further exploratory subset analyses that evaluated the effects of genomic parameters known to impact patient responses to anti-EGFR monoclonal antibodies. Removal of the outlier Russian subpopulation of patients provided a patient population that was more homogeneous with respect to their prior treatment regimens, thereby facilitating further exploratory analyses. If a subject had not died, survival time was censored at the last date the subject was known to be alive.

Time Frame From randomization until the date of death (assessed up to 32 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was the EU+US TNmCRC analysis set, which is a genomically-defined subpopulation excluding DNmCRC patients with six (6) selected EGFR extracellular domain (ECD) mutations.
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Hide Arm/Group Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Overall Number of Participants Analyzed 47 46 38
Median (95% Confidence Interval)
Unit of Measure: months
10.6
(6.8 to 13.1)
12.8
(9.7 to 14.7)
7.3
(6.3 to 8.8)
Time Frame Adverse event (AE) data were collected beginning with the signing of informed consent and continued through the End of Trial Intervention Visit (i.e., no earlier than 28 days after stop of treatment). The AE data collection period was 38 months.
Adverse Event Reporting Description Subjects analyzed for the Serious Adverse Events and Other (Not Including Serious) Adverse Events tables are based on the Safety Analysis Set. The Safety Analysis Set contained all subjects in the Intent-to-Treat (ITT) Analysis Set who received at least one (1) dose of trial treatment (Sym004, 5-FU, or capecitabine) and in addition, those subjects who received Best Supportive Care only. The All-Cause Mortality table also includes those subjects who were randomized but not treated.
 
Arm/Group Title Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Hide Arm/Group Description

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (12 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Sym004 (9/6 mg/kg): Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR.

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Best Supportive Care (BSC): BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support.

Fluorouracil (5-FU): 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Capecitabine: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

All-Cause Mortality
Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   68/83 (81.93%)   62/86 (72.09%)   57/85 (67.06%) 
Show Serious Adverse Events Hide Serious Adverse Events
Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   27/83 (32.53%)   23/84 (27.38%)   12/78 (15.38%) 
Blood and lymphatic system disorders       
Thrombocytopenia  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Cardiac disorders       
Acute coronary syndrome  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Cardiac arrest  1  0/83 (0.00%)  0/84 (0.00%)  1/78 (1.28%) 
Cardiac failure  1  0/83 (0.00%)  0/84 (0.00%)  1/78 (1.28%) 
Sinus node dysfunction  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  2/83 (2.41%)  1/84 (1.19%)  2/78 (2.56%) 
Intestinal obstruction  1  2/83 (2.41%)  2/84 (2.38%)  1/78 (1.28%) 
Vomiting  1  2/83 (2.41%)  0/84 (0.00%)  3/78 (3.85%) 
Colitis  1  0/83 (0.00%)  0/84 (0.00%)  1/78 (1.28%) 
Oesophageal varices haemorrhage  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Pancreatitis acute  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Rectal obstruction  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
General disorders       
Pyrexia  1  2/83 (2.41%)  2/84 (2.38%)  0/78 (0.00%) 
Asthenia  1  1/83 (1.20%)  1/84 (1.19%)  0/78 (0.00%) 
General physical health deterioration  1  2/83 (2.41%)  0/84 (0.00%)  0/78 (0.00%) 
Oedema peripheral  1  0/83 (0.00%)  2/84 (2.38%)  0/78 (0.00%) 
Chest pain  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Hyperthermia  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Hepatobiliary disorders       
Jaundice cholestatic  1  0/83 (0.00%)  1/84 (1.19%)  1/78 (1.28%) 
Hepatic function abnormal  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Hepatorenal syndrome  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Infections and infestations       
Device related infection  1  1/83 (1.20%)  2/84 (2.38%)  1/78 (1.28%) 
Pneumonia  1  2/83 (2.41%)  1/84 (1.19%)  0/78 (0.00%) 
Sepsis  1  1/83 (1.20%)  1/84 (1.19%)  0/78 (0.00%) 
Urinary tract infection  1  1/83 (1.20%)  1/84 (1.19%)  0/78 (0.00%) 
Abdominal abscess  1  0/83 (0.00%)  0/84 (0.00%)  1/78 (1.28%) 
Bacteraemia  1  0/83 (0.00%)  0/84 (0.00%)  1/78 (1.28%) 
Device related sepsis  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Impetigo  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Staphylococcal sepsis  1  0/83 (0.00%)  0/84 (0.00%)  1/78 (1.28%) 
Urosepsis  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Injury, poisoning and procedural complications       
Infusion related reaction  1  2/83 (2.41%)  1/84 (1.19%)  0/78 (0.00%) 
Rib fracture  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Spinal compression fracture  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Urinary tract stoma complication  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Metabolism and nutrition disorders       
Hypomagnesaemia  1  4/83 (4.82%)  5/84 (5.95%)  0/78 (0.00%) 
Dehydration  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Electrolyte imbalance  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  1/83 (1.20%)  0/84 (0.00%)  1/78 (1.28%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Metastases to central nervous system  1  0/83 (0.00%)  0/84 (0.00%)  1/78 (1.28%) 
Tumour associated fever  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Tumour haemorrhage  1  0/83 (0.00%)  0/84 (0.00%)  1/78 (1.28%) 
Nervous system disorders       
Seizure  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Renal and urinary disorders       
Acute kidney injury  1  0/83 (0.00%)  1/84 (1.19%)  1/78 (1.28%) 
Hydronephrosis  1  0/83 (0.00%)  0/84 (0.00%)  1/78 (1.28%) 
Renal failure  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Vesicocutaneous fistula  1  0/83 (0.00%)  0/84 (0.00%)  1/78 (1.28%) 
Reproductive system and breast disorders       
Pelvic pain  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Dyspnoea  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Pleural effusion  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Pneumonia aspiration  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Pneumothorax  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Pulmonary embolism  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Respiratory failure  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Skin and subcutaneous tissue disorders       
Blister  1  0/83 (0.00%)  1/84 (1.19%)  0/78 (0.00%) 
Erythema  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
Skin toxicity  1  1/83 (1.20%)  0/84 (0.00%)  0/78 (0.00%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A: Sym004 (12 mg/kg) Arm B: Sym004 (9/6 mg/kg) Arm C: Investigator's Choice
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   83/83 (100.00%)   84/84 (100.00%)   67/78 (85.90%) 
Blood and lymphatic system disorders       
Anaemia  1  10/83 (12.05%)  15/84 (17.86%)  11/78 (14.10%) 
Thrombocytopenia  1  3/83 (3.61%)  7/84 (8.33%)  8/78 (10.26%) 
Leukopenia  1  4/83 (4.82%)  7/84 (8.33%)  5/78 (6.41%) 
Neutropenia  1  2/83 (2.41%)  4/84 (4.76%)  9/78 (11.54%) 
Cardiac disorders       
Sinus tachycardia  1  7/83 (8.43%)  11/84 (13.10%)  7/78 (8.97%) 
Supraventricular extrasystoles  1  1/83 (1.20%)  5/84 (5.95%)  2/78 (2.56%) 
Gastrointestinal disorders       
Diarrhoea  1  10/83 (12.05%)  19/84 (22.62%)  20/78 (25.64%) 
Abdominal pain  1  13/83 (15.66%)  10/84 (11.90%)  3/78 (3.85%) 
Nausea  1  9/83 (10.84%)  10/84 (11.90%)  12/78 (15.38%) 
Vomiting  1  6/83 (7.23%)  4/84 (4.76%)  6/78 (7.69%) 
Constipation  1  6/83 (7.23%)  3/84 (3.57%)  6/78 (7.69%) 
Stomatitis  1  8/83 (9.64%)  4/84 (4.76%)  0/78 (0.00%) 
Abdominal pain upper  1  2/83 (2.41%)  0/84 (0.00%)  4/78 (5.13%) 
General disorders       
Asthenia  1  26/83 (31.33%)  21/84 (25.00%)  14/78 (17.95%) 
Xerosis  1  26/83 (31.33%)  12/84 (14.29%)  0/78 (0.00%) 
Pyrexia  1  12/83 (14.46%)  10/84 (11.90%)  9/78 (11.54%) 
Fatigue  1  8/83 (9.64%)  7/84 (8.33%)  14/78 (17.95%) 
Oedema peripheral  1  9/83 (10.84%)  7/84 (8.33%)  1/78 (1.28%) 
Mucosal inflammation  1  8/83 (9.64%)  6/84 (7.14%)  4/78 (5.13%) 
Chills  1  3/83 (3.61%)  5/84 (5.95%)  1/78 (1.28%) 
Infections and infestations       
Paronychia  1  15/83 (18.07%)  18/84 (21.43%)  3/78 (3.85%) 
Conjunctivitis  1  13/83 (15.66%)  8/84 (9.52%)  1/78 (1.28%) 
Urinary tract infection  1  5/83 (6.02%)  3/84 (3.57%)  1/78 (1.28%) 
Upper respiratory tract infection  1  1/83 (1.20%)  5/84 (5.95%)  0/78 (0.00%) 
Injury, poisoning and procedural complications       
Infusion related reaction  1  18/83 (21.69%)  15/84 (17.86%)  0/78 (0.00%) 
Investigations       
Blood alkaline phosphatase increased  1  7/83 (8.43%)  10/84 (11.90%)  6/78 (7.69%) 
Alanine aminotransferase increased  1  7/83 (8.43%)  8/84 (9.52%)  0/78 (0.00%) 
Aspartate aminotransferase increased  1  8/83 (9.64%)  6/84 (7.14%)  1/78 (1.28%) 
Electrocardiogram QT prolonged  1  6/83 (7.23%)  7/84 (8.33%)  2/78 (2.56%) 
Blood bilirubin increased  1  5/83 (6.02%)  2/84 (2.38%)  1/78 (1.28%) 
Metabolism and nutrition disorders       
Hypomagnesaemia  1  57/83 (68.67%)  47/84 (55.95%)  6/78 (7.69%) 
Decreased appetite  1  20/83 (24.10%)  9/84 (10.71%)  7/78 (8.97%) 
Hypocalcaemia  1  9/83 (10.84%)  8/84 (9.52%)  2/78 (2.56%) 
Hypokalaemia  1  10/83 (12.05%)  4/84 (4.76%)  3/78 (3.85%) 
Hyperglycaemia  1  4/83 (4.82%)  5/84 (5.95%)  2/78 (2.56%) 
Hypoalbuminaemia  1  3/83 (3.61%)  5/84 (5.95%)  1/78 (1.28%) 
Hyperkalaemia  1  1/83 (1.20%)  5/84 (5.95%)  0/78 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  5/83 (6.02%)  5/84 (5.95%)  7/78 (8.97%) 
Muscle spasms  1  3/83 (3.61%)  5/84 (5.95%)  1/78 (1.28%) 
Psychiatric disorders       
Insomnia  1  9/83 (10.84%)  2/84 (2.38%)  0/78 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  5/83 (6.02%)  3/84 (3.57%)  6/78 (7.69%) 
Cough  1  3/83 (3.61%)  5/84 (5.95%)  5/78 (6.41%) 
Skin and subcutaneous tissue disorders       
Dermatitis acneiform  1  68/83 (81.93%)  65/84 (77.38%)  1/78 (1.28%) 
Pruritus  1  33/83 (39.76%)  30/84 (35.71%)  2/78 (2.56%) 
Skin fissures  1  14/83 (16.87%)  16/84 (19.05%)  2/78 (2.56%) 
Erythema  1  16/83 (19.28%)  11/84 (13.10%)  0/78 (0.00%) 
Dry skin  1  8/83 (9.64%)  10/84 (11.90%)  1/78 (1.28%) 
Palmar-plantar erythrodysaesthesia syndrome  1  1/83 (1.20%)  1/84 (1.19%)  14/78 (17.95%) 
Photosensitivity reaction  1  10/83 (12.05%)  4/84 (4.76%)  0/78 (0.00%) 
Rash  1  7/83 (8.43%)  6/84 (7.14%)  0/78 (0.00%) 
Vascular disorders       
Hypertension  1  6/83 (7.23%)  2/84 (2.38%)  1/78 (1.28%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Considering the hypothesis-generating nature of a phase 2 clinical trial, the intent-to-treat (ITT) analysis should be viewed as the starting point of a scientific investigation process, not the final conclusion.
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.
The investigator will inform the sponsor in advance about any plans to publish or present data from the trial. Any publications and presentations of the results (abstracts in journals or newspapers, oral presentations, etc.), either in whole or in part, by investigators or their representatives will require pre-submission review by the sponsor. The sponsor will not suppress or veto publications, but maintains the right to delay publication in order to protect intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Scientific Officer
Organization: Symphogen A/S
Phone: +45 8838 2600
EMail: info@symphogen.com
Publications:
Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A, on behalf of the EORTC Quality of Life Group. The EORTC QLQ-C30 Scoring Manual (3rd Edition). Published by: European Organisation for Research and Treatment of Cancer, Brussels 2001.
Layout table for additonal information
Responsible Party: Symphogen A/S
ClinicalTrials.gov Identifier: NCT02083653     History of Changes
Other Study ID Numbers: Sym004-05
2013-003829-29 ( EudraCT Number )
EMR200637-002 ( Other Identifier: Merck KGaA )
First Submitted: March 7, 2014
First Posted: March 11, 2014
Results First Submitted: September 12, 2018
Results First Posted: December 24, 2018
Last Update Posted: April 16, 2019