Trial Outcomes & Findings for Sym004 vs Standard of Care in Subjects With Metastatic Colorectal Cancer (NCT NCT02083653)

NCT ID: NCT02083653

Last Updated: 2019-04-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

254 participants

Primary outcome timeframe

From randomization until the date of death (assessed up to 32 months).

Results posted on

2019-04-16

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A: Sym004 (12 mg/kg) 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).	Arm B: Sym004 (9/6 mg/kg) 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.	Arm C: Investigator's Choice 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 Study STARTED	83	86	85
Overall Study COMPLETED	1	1	1
Overall Study NOT COMPLETED	82	85	84

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Sym004 (12 mg/kg) 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).	Arm B: Sym004 (9/6 mg/kg) 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.	Arm C: Investigator's Choice 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 Study Randomized but not Treated	0	2	7
Overall Study Adverse Event	12	5	4
Overall Study Lost to Follow-up	1	0	0
Overall Study Death	2	2	2
Overall Study Progressive Disease	65	73	63
Overall Study Withdrawal by Subject	2	1	2
Overall Study Other Events	0	2	2
Overall Study Reason Missing	0	0	4

Baseline Characteristics

The age summary does not include subjects living in Germany.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Sym004 (12 mg/kg) n=83 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=86 Participants 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.	Arm C: Investigator's Choice n=85 Participants 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 n=254 Participants Total of all reporting groups
Age, Continuous	62.2 years STANDARD_DEVIATION 9.91 • n=79 Participants • The age summary does not include subjects living in Germany.	64.2 years STANDARD_DEVIATION 10.41 • n=86 Participants • The age summary does not include subjects living in Germany.	61.4 years STANDARD_DEVIATION 10.70 • n=84 Participants • The age summary does not include subjects living in Germany.	62.6 years STANDARD_DEVIATION 10.38 • n=249 Participants • The age summary does not include subjects living in Germany.
Sex: Female, Male Female	31 Participants n=83 Participants	32 Participants n=86 Participants	31 Participants n=85 Participants	94 Participants n=254 Participants
Sex: Female, Male Male	52 Participants n=83 Participants	54 Participants n=86 Participants	54 Participants n=85 Participants	160 Participants n=254 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=83 Participants	5 Participants n=86 Participants	5 Participants n=85 Participants	15 Participants n=254 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	69 Participants n=83 Participants	72 Participants n=86 Participants	70 Participants n=85 Participants	211 Participants n=254 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=83 Participants	9 Participants n=86 Participants	10 Participants n=85 Participants	28 Participants n=254 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=83 Participants	0 Participants n=86 Participants	0 Participants n=85 Participants	0 Participants n=254 Participants
Race (NIH/OMB) Asian	1 Participants n=83 Participants	0 Participants n=86 Participants	0 Participants n=85 Participants	1 Participants n=254 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=83 Participants	0 Participants n=86 Participants	0 Participants n=85 Participants	0 Participants n=254 Participants
Race (NIH/OMB) Black or African American	1 Participants n=83 Participants	2 Participants n=86 Participants	0 Participants n=85 Participants	3 Participants n=254 Participants
Race (NIH/OMB) White	72 Participants n=83 Participants	75 Participants n=86 Participants	73 Participants n=85 Participants	220 Participants n=254 Participants
Race (NIH/OMB) More than one race	0 Participants n=83 Participants	0 Participants n=86 Participants	0 Participants n=85 Participants	0 Participants n=254 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=83 Participants	9 Participants n=86 Participants	12 Participants n=85 Participants	30 Participants n=254 Participants
Region of Enrollment Austria	0 participants n=83 Participants	1 participants n=86 Participants	1 participants n=85 Participants	2 participants n=254 Participants
Region of Enrollment Belgium	3 participants n=83 Participants	6 participants n=86 Participants	5 participants n=85 Participants	14 participants n=254 Participants
Region of Enrollment Hungary	0 participants n=83 Participants	1 participants n=86 Participants	5 participants n=85 Participants	6 participants n=254 Participants
Region of Enrollment United States	8 participants n=83 Participants	6 participants n=86 Participants	8 participants n=85 Participants	22 participants n=254 Participants
Region of Enrollment Poland	10 participants n=83 Participants	8 participants n=86 Participants	7 participants n=85 Participants	25 participants n=254 Participants
Region of Enrollment Italy	17 participants n=83 Participants	12 participants n=86 Participants	20 participants n=85 Participants	49 participants n=254 Participants
Region of Enrollment France	9 participants n=83 Participants	9 participants n=86 Participants	10 participants n=85 Participants	28 participants n=254 Participants
Region of Enrollment Germany	4 participants n=83 Participants	0 participants n=86 Participants	1 participants n=85 Participants	5 participants n=254 Participants
Region of Enrollment Russia	8 participants n=83 Participants	12 participants n=86 Participants	10 participants n=85 Participants	30 participants n=254 Participants
Region of Enrollment Spain	24 participants n=83 Participants	31 participants n=86 Participants	18 participants n=85 Participants	73 participants n=254 Participants
Height	168.9 centimeters (cm) STANDARD_DEVIATION 10.82 • n=83 Participants	169.1 centimeters (cm) STANDARD_DEVIATION 9.71 • n=86 Participants	167.9 centimeters (cm) STANDARD_DEVIATION 9.56 • n=85 Participants	168.7 centimeters (cm) STANDARD_DEVIATION 10.01 • n=254 Participants
Weight	75.3 kilograms (kg) STANDARD_DEVIATION 13.51 • n=83 Participants	74.0 kilograms (kg) STANDARD_DEVIATION 14.14 • n=86 Participants	76.0 kilograms (kg) STANDARD_DEVIATION 16.13 • n=85 Participants	75.1 kilograms (kg) STANDARD_DEVIATION 14.61 • n=254 Participants
Body Mass Index (BMI)	26.5 kg/m^2 STANDARD_DEVIATION 4.43 • n=83 Participants	25.8 kg/m^2 STANDARD_DEVIATION 4.26 • n=86 Participants	26.8 kg/m^2 STANDARD_DEVIATION 4.59 • n=85 Participants	26.4 kg/m^2 STANDARD_DEVIATION 4.43 • n=254 Participants

PRIMARY outcome

Timeframe: From randomization until the date of death (assessed up to 32 months).

Population: 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.

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=83 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=86 Participants 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.	Arm C: Investigator's Choice n=85 Participants 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 Survival (OS) Time	7.9 months Interval 6.5 to 9.9	10.3 months Interval 9.0 to 12.9	9.6 months Interval 8.3 to 12.2

SECONDARY outcome

Timeframe: 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).

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=83 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=86 Participants 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.	Arm C: Investigator's Choice n=85 Participants 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.
Best Overall Response (OR) According to the Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Complete Response (CR)	0 Participants	0 Participants	1 Participants
Best Overall Response (OR) According to the Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Partial Response (PR)	11 Participants	8 Participants	1 Participants
Best Overall Response (OR) According to the Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Stable Disease (SD)	40 Participants	47 Participants	37 Participants
Best Overall Response (OR) According to the Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Progressive Disease (PD)	27 Participants	28 Participants	31 Participants
Best Overall Response (OR) According to the Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Not Evaluable (NE)	5 Participants	3 Participants	15 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=83 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=86 Participants 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.	Arm C: Investigator's Choice n=85 Participants 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.
Progression Free Survival (PFS) Time	2.8 months Interval 1.8 to 3.2	2.7 months Interval 2.6 to 3.3	2.6 months Interval 1.4 to 3.1

SECONDARY outcome

Timeframe: From randomization until treatment discontinuation for any reason, including disease progression or death (assessed up to 32 months).

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

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=83 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=86 Participants 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.	Arm C: Investigator's Choice n=85 Participants 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.
Time to Treatment Failure (TTF)	2.1 months Interval 1.4 to 2.7	2.6 months Interval 2.2 to 2.6	1.6 months Interval 1.2 to 2.7

SECONDARY outcome

Timeframe: From Baseline up to 28 days after the last IMP administration.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=83 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=84 Participants 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.	Arm C: Investigator's Choice n=78 Participants 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.
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). Related TEAE leading to interruption of treatment	53 Participants	42 Participants	7 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). Related TEAE leading to treatment withdrawal	9 Participants	2 Participants	3 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least one Serious TEAE	27 Participants	23 Participants	12 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). TEAE leading to interruption of trial treatment	58 Participants	47 Participants	10 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). TEAE leading to trial treatment withdrawal	12 Participants	5 Participants	6 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). TEAE related to trial treatment	81 Participants	80 Participants	46 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). TEAE, Grade >=3	67 Participants	53 Participants	25 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). TEAE resulting in death	4 Participants	4 Participants	3 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). Related Serious TEAE	9 Participants	6 Participants	2 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). Related TEAE leading to dose reduction	29 Participants	17 Participants	6 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). Related TEAE, Grade >=3	58 Participants	41 Participants	9 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). Related TEAE resulting in death	0 Participants	0 Participants	0 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least one TEAE	83 Participants	84 Participants	67 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). TEAE leading to dose reduction	29 Participants	17 Participants	8 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). Dermatologic toxicity	78 Participants	78 Participants	8 Participants
Occurrence and Nature of Adverse Events (AEs), as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). Infusion-related reaction	27 Participants	26 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug until disease progression (assessed up to 32 months).

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=83 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=84 Participants 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.	Arm C: Investigator's Choice 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.
Relative Dose Intensity of Sym004	80.49 percentage of relative dose intensity Standard Deviation 20.020	88.91 percentage of relative dose intensity Standard Deviation 13.843	—

SECONDARY outcome

Timeframe: Weeks 3, 5, and 7 and at the End of Treatment visit, including a Week 1 and Week 2 subset.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=80 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=83 Participants 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.	Arm C: Investigator's Choice 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.
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 1 Day 1 (1 hour after EOI)	209.80 ug/mL Standard Deviation 60.707	189.24 ug/mL Standard Deviation 38.923	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 1 Day 1 (0.5 hours after EOI)	214.98 ug/mL Standard Deviation 46.242	184.84 ug/mL Standard Deviation 33.103	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Screening (Pre-dose)	0.50 ug/mL Standard Deviation 0.000	0.50 ug/mL Standard Deviation 0.000	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 1 Day 1 (Pre-dose)	0.50 ug/mL Standard Deviation 0.000	0.75 ug/mL Standard Deviation 0.700	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 1 Day 1 (EOI)	182.95 ug/mL Standard Deviation 97.686	174.44 ug/mL Standard Deviation 47.023	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 1 Day 1 (2 hours after EOI)	197.31 ug/mL Standard Deviation 65.801	181.68 ug/mL Standard Deviation 37.577	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 1 Day 1 (4 hours after EOI)	188.75 ug/mL Standard Deviation 68.421	171.63 ug/mL Standard Deviation 35.862	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 2 Day 1 (Pre-dose)	45.37 ug/mL Standard Deviation 28.604	38.76 ug/mL Standard Deviation 10.311	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 2 Day 1 (EOI)	275.42 ug/mL Standard Deviation 80.975	145.91 ug/mL Standard Deviation 47.950	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 3 Day 1 (Pre-dose)	92.66 ug/mL Standard Deviation 38.443	44.26 ug/mL Standard Deviation 20.995	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 3 Day 1 (EOI)	323.35 ug/mL Standard Deviation 83.412	170.18 ug/mL Standard Deviation 50.323	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 5 Day 1 (Pre-dose)	125.73 ug/mL Standard Deviation 61.644	49.26 ug/mL Standard Deviation 30.252	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 5 Day 1 (EOI)	354.91 ug/mL Standard Deviation 108.263	168.94 ug/mL Standard Deviation 67.901	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 7 Day 1 (Pre-dose)	128.30 ug/mL Standard Deviation 77.437	58.38 ug/mL Standard Deviation 47.505	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations Week 7 Day 1 (EOI)	346.83 ug/mL Standard Deviation 136.083	163.11 ug/mL Standard Deviation 74.967	—
Pharmacokinetic (PK) Parameters: Sym004 Concentrations End of Treatment	64.55 ug/mL Standard Deviation 79.250	17.61 ug/mL Standard Deviation 24.474	—

SECONDARY outcome

Timeframe: Day 1 on Weeks 1-3 followed by Week 5 Day 1 and Week 7 Day 1.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=80 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=83 Participants 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.	Arm C: Investigator's Choice 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.
Pharmacokinetic (PK) Parameters: Time of Maximum Plasma Concentration (Tmax) Week 1 Day 1	3.14 hours Standard Deviation 0.822	2.79 hours Standard Deviation 0.210	—
Pharmacokinetic (PK) Parameters: Time of Maximum Plasma Concentration (Tmax) Week 2 Day 1	2.82 hours Standard Deviation 0.306	2.33 hours Standard Deviation 0.459	—
Pharmacokinetic (PK) Parameters: Time of Maximum Plasma Concentration (Tmax) Week 3 Day 1	3.01 hours Standard Deviation 0.555	2.34 hours Standard Deviation 0.477	—
Pharmacokinetic (PK) Parameters: Time of Maximum Plasma Concentration (Tmax) Week 5 Day 1	2.74 hours Standard Deviation 0.532	2.06 hours Standard Deviation 0.448	—
Pharmacokinetic (PK) Parameters: Time of Maximum Plasma Concentration (Tmax) Week 7 Day 1	2.83 hours Standard Deviation 0.867	2.06 hours Standard Deviation 0.473	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=83 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=84 Participants 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.	Arm C: Investigator's Choice 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.
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Screening · Negative	78 Participants	81 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Screening · Positive	2 Participants	0 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Screening · Not Reportable	1 Participants	0 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Screening · Missing	2 Participants	3 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 5 Day 1 · Negative	59 Participants	62 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 5 Day 1 · Positive	0 Participants	0 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 5 Day 1 · Not Reportable	0 Participants	0 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 5 Day 1 · Missing	24 Participants	22 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 12 · Negative	24 Participants	35 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 12 · Positive	0 Participants	0 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 12 · Not Reportable	0 Participants	0 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 12 · Missing	59 Participants	49 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 13 · Negative	1 Participants	1 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 13 · Positive	0 Participants	0 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 13 · Not Reportable	0 Participants	0 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 13 · Missing	82 Participants	83 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 24 · Negative	0 Participants	1 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 24 · Positive	0 Participants	0 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 24 · Not Reportable	0 Participants	0 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time Week 24 · Missing	83 Participants	83 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time End of Treatment Visit · Negative	60 Participants	55 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time End of Treatment Visit · Positive	0 Participants	0 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time End of Treatment Visit · Not Reportable	0 Participants	0 Participants	—
Host Immune Response: Number of Subjects With Anti-drug Antibodies (ADAs) to Sym004 Over Time End of Treatment Visit · Missing	23 Participants	29 Participants	—

SECONDARY outcome

Timeframe: Assessed every 6 weeks (week 1 and week 7 reported)

Population: 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.

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).

Outcome measures

SECONDARY outcome

Timeframe: Assessed every 6 weeks (week 1 and week 7 reported)

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).

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=83 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=86 Participants 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.	Arm C: Investigator's Choice n=85 Participants 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.
Quality of Life Assessed by EORTC QLQ-CR29 Sore Skin (Week 7 Day 1)	11.6 score on a scale Interval 0.0 to 33.0	9.7 score on a scale Interval 0.0 to 67.0	4.2 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by EORTC QLQ-CR29 Body Image (Week 1 Day 1)	76.2 score on a scale Interval 0.0 to 100.0	80.1 score on a scale Interval 0.0 to 100.0	75.8 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Anxiety (Week 7 Day 1)	57.1 score on a scale Interval 0.0 to 100.0	61.1 score on a scale Interval 0.0 to 100.0	50.9 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Weight (Week 1 Day 1)	79.5 score on a scale Interval 0.0 to 100.0	85.6 score on a scale Interval 0.0 to 100.0	78.3 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Weight (Week 7 Day 1)	86.6 score on a scale Interval 33.0 to 100.0	89.6 score on a scale Interval 33.0 to 100.0	88.0 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Sexual Function (Men) (Week 1 Day 1)	31.7 score on a scale Interval 0.0 to 100.0	21.2 score on a scale Interval 0.0 to 100.0	23.5 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Sexual Function (Men) (Week 7 Day 1)	33.2 score on a scale Interval 0.0 to 100.0	26.6 score on a scale Interval 0.0 to 67.0	34.9 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Sexual Function (Women) (Week 1 Day 1)	16.5 score on a scale Interval 0.0 to 33.0	12.3 score on a scale Interval 0.0 to 67.0	10.1 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by EORTC QLQ-CR29 Sexual Function (Women) (Week 7 Day 1)	16.6 score on a scale Interval 0.0 to 67.0	13.6 score on a scale Interval 0.0 to 67.0	11.0 score on a scale Interval 0.0 to 33.0
Quality of Life Assessed by EORTC QLQ-CR29 Urinary Frequency (Week 1 Day 1)	34.4 score on a scale Interval 0.0 to 100.0	30.3 score on a scale Interval 0.0 to 83.0	32.6 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Urinary Frequency (Week 7 Day 1)	28.2 score on a scale Interval 0.0 to 100.0	28.8 score on a scale Interval 0.0 to 67.0	18.5 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by EORTC QLQ-CR29 Blood and Mucus (Week 1 Day 1)	4.1 score on a scale Interval 0.0 to 50.0	1.5 score on a scale Interval 0.0 to 33.0	2.0 score on a scale Interval 0.0 to 33.0
Quality of Life Assessed by EORTC QLQ-CR29 Blood and Mucus (Week 7 Day 1)	2.6 score on a scale Interval 0.0 to 33.0	3.1 score on a scale Interval 0.0 to 67.0	2.3 score on a scale Interval 0.0 to 33.0
Quality of Life Assessed by EORTC QLQ-CR29 Urinary Incontinence (Week 7 Day 1)	7.0 score on a scale Interval 0.0 to 67.0	4.8 score on a scale Interval 0.0 to 67.0	1.9 score on a scale Interval 0.0 to 33.0
Quality of Life Assessed by EORTC QLQ-CR29 Dysuria (Week 1 Day 1)	4.0 score on a scale Interval 0.0 to 33.0	2.9 score on a scale Interval 0.0 to 67.0	3.0 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by EORTC QLQ-CR29 Dysuria (Week 7 Day 1)	3.2 score on a scale Interval 0.0 to 33.0	2.1 score on a scale Interval 0.0 to 33.0	0.9 score on a scale Interval 0.0 to 33.0
Quality of Life Assessed by EORTC QLQ-CR29 Abdominal Pain (Week 1 Day 1)	18.8 score on a scale Interval 0.0 to 100.0	12.8 score on a scale Interval 0.0 to 100.0	23.0 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Buttock Pain (Week 1 Day 1)	11.6 score on a scale Interval 0.0 to 100.0	10.8 score on a scale Interval 0.0 to 100.0	9.9 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Bloated Feeling (Week 7 Day 1)	13.3 score on a scale Interval 0.0 to 67.0	12.1 score on a scale Interval 0.0 to 33.0	12.9 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by EORTC QLQ-CR29 Flatulence (Week 1 Day 1)	18.3 score on a scale Interval 0.0 to 100.0	19.5 score on a scale Interval 0.0 to 100.0	23.1 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Faecal Incontinence (Week 1 Day 1)	8.9 score on a scale Interval 0.0 to 100.0	8.8 score on a scale Interval 0.0 to 100.0	7.1 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by EORTC QLQ-CR29 Body Image (Week 7 Day 1)	76.4 score on a scale Interval 11.0 to 100.0	77.6 score on a scale Interval 33.0 to 100.0	78.2 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Anxiety (Week 1 Day 1)	50.0 score on a scale Interval 0.0 to 100.0	48.2 score on a scale Interval 0.0 to 100.0	43.0 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Stool Frequency (Week 1 Day 1)	15.5 score on a scale Interval 0.0 to 100.0	11.3 score on a scale Interval 0.0 to 100.0	14.1 score on a scale Interval 0.0 to 83.0
Quality of Life Assessed by EORTC QLQ-CR29 Stool Frequency (Week 7 Day 1)	13.4 score on a scale Interval 0.0 to 50.0	11.8 score on a scale Interval 0.0 to 83.0	13.1 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by EORTC QLQ-CR29 Urinary Incontinence (Week 1 Day 1)	8.2 score on a scale Interval 0.0 to 100.0	7.5 score on a scale Interval 0.0 to 100.0	7.4 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Abdominal Pain (Week 7 Day 1)	10.4 score on a scale Interval 0.0 to 67.0	10.8 score on a scale Interval 0.0 to 67.0	16.6 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by EORTC QLQ-CR29 Buttock Pain (Week 7 Day 1)	4.4 score on a scale Interval 0.0 to 33.0	8.8 score on a scale Interval 0.0 to 67.0	7.4 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by EORTC QLQ-CR29 Bloated Feeling (Week 1 Day 1)	20.4 score on a scale Interval 0.0 to 100.0	14.8 score on a scale Interval 0.0 to 67.0	21.7 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Dry Mouth (Weel 1 Day 1)	25.1 score on a scale Interval 0.0 to 100.0	17.0 score on a scale Interval 0.0 to 67.0	22.1 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Dry Mouth (Weel 7 Day 1)	26.8 score on a scale Interval 0.0 to 100.0	29.2 score on a scale Interval 0.0 to 100.0	13.8 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by EORTC QLQ-CR29 Hair Loss (Week 1 Day 1)	17.1 score on a scale Interval 0.0 to 100.0	11.1 score on a scale Interval 0.0 to 100.0	14.6 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Hair Loss (Week 7 Day 1)	7.0 score on a scale Interval 0.0 to 100.0	7.6 score on a scale Interval 0.0 to 67.0	4.6 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Trouble with Taste (Week 1 Day 1)	20.0 score on a scale Interval 0.0 to 100.0	13.9 score on a scale Interval 0.0 to 100.0	15.1 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Trouble with Taste (Week 7 Day 1)	18.5 score on a scale Interval 0.0 to 100.0	15.2 score on a scale Interval 0.0 to 67.0	12.9 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Flatulence (Week 7 Day 1)	12.4 score on a scale Interval 0.0 to 67.0	16.1 score on a scale Interval 0.0 to 67.0	12.4 score on a scale Interval 0.0 to 33.0
Quality of Life Assessed by EORTC QLQ-CR29 Faecal Incontinence (Week 7 Day 1)	2.5 score on a scale Interval 0.0 to 33.0	7.3 score on a scale Interval 0.0 to 67.0	3.1 score on a scale Interval 0.0 to 33.0
Quality of Life Assessed by EORTC QLQ-CR29 Sore Skin (Week 1 Day 1)	9.6 score on a scale Interval 0.0 to 67.0	8.8 score on a scale Interval 0.0 to 67.0	6.0 score on a scale Interval 0.0 to 33.0
Quality of Life Assessed by EORTC QLQ-CR29 Embarrassed by Bowel Movement (Week 1 Day 1)	8.5 score on a scale Interval 0.0 to 100.0	7.8 score on a scale Interval 0.0 to 100.0	13.9 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Embarrassed by Bowel Movement (Week 7 Day 1)	7.5 score on a scale Interval 0.0 to 67.0	8.1 score on a scale Interval 0.0 to 67.0	10.4 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by EORTC QLQ-CR29 Stoma Care Problem (Week 1 Day 1)	16.6 score on a scale Interval 0.0 to 100.0	3.3 score on a scale Interval 0.0 to 33.0	6.6 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by EORTC QLQ-CR29 Stoma Care Problem (Week 7 Day 1)	9.9 score on a scale Interval 0.0 to 33.0	2.4 score on a scale Interval 0.0 to 33.0	8.3 score on a scale Interval 0.0 to 33.0
Quality of Life Assessed by EORTC QLQ-CR29 Impotence (Week 1 Day 1)	46.9 score on a scale Interval 0.0 to 100.0	38.7 score on a scale Interval 0.0 to 100.0	49.5 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Impotence (Week 7 Day 1)	40.4 score on a scale Interval 0.0 to 100.0	42.7 score on a scale Interval 0.0 to 100.0	50.7 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Dyspareunia (Week 1 Day 1)	12.1 score on a scale Interval 0.0 to 100.0	7.2 score on a scale Interval 0.0 to 33.0	11.0 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by EORTC QLQ-CR29 Dyspareunia (Week 7 Day 1)	14.3 score on a scale Interval 0.0 to 67.0	10.3 score on a scale Interval 0.0 to 33.0	13.3 score on a scale Interval 0.0 to 67.0

SECONDARY outcome

Timeframe: Assessed every 3 weeks (week 1 and week 4 reported)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=83 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=86 Participants 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.	Arm C: Investigator's Choice n=85 Participants 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.
Quality of Life Assessed by FACT-EGFRI-18 for Skin Rash Social/Emotional (Week 1 Day 1)	21.5 score on a scale Interval 9.0 to 24.0	21.5 score on a scale Interval 6.0 to 24.0	22.6 score on a scale Interval 9.0 to 24.0
Quality of Life Assessed by FACT-EGFRI-18 for Skin Rash Symptom Index (Week 1 Day 1)	62.3 score on a scale Interval 18.0 to 72.0	62.9 score on a scale Interval 20.0 to 72.0	65.6 score on a scale Interval 19.0 to 72.0
Quality of Life Assessed by FACT-EGFRI-18 for Skin Rash Physical (Week 1 Day 1)	22.9 score on a scale Interval 2.0 to 28.0	23.1 score on a scale Interval 4.0 to 28.0	24.3 score on a scale Interval 6.0 to 28.0
Quality of Life Assessed by FACT-EGFRI-18 for Skin Rash Physical (Week 4 Day 1)	18.0 score on a scale Interval 4.0 to 28.0	19.7 score on a scale Interval 5.0 to 28.0	25.1 score on a scale Interval 16.0 to 28.0
Quality of Life Assessed by FACT-EGFRI-18 for Skin Rash Social/Emotional (Week 4 Day 1)	19.9 score on a scale Interval 7.0 to 24.0	20.3 score on a scale Interval 5.0 to 24.0	23.2 score on a scale Interval 15.0 to 24.0
Quality of Life Assessed by FACT-EGFRI-18 for Skin Rash Functional (Week 1 Day 1)	17.9 score on a scale Interval 5.0 to 20.0	18.3 score on a scale Interval 7.0 to 20.0	18.7 score on a scale Interval 4.0 to 20.0
Quality of Life Assessed by FACT-EGFRI-18 for Skin Rash Functional (Week 4 Day 1)	16.3 score on a scale Interval 3.0 to 20.0	17.0 score on a scale Interval 6.0 to 20.0	19.3 score on a scale Interval 13.0 to 20.0
Quality of Life Assessed by FACT-EGFRI-18 for Skin Rash Symptom Index (Week 4 Day 1)	54.2 score on a scale Interval 16.0 to 72.0	57.0 score on a scale Interval 22.0 to 72.0	67.6 score on a scale Interval 46.0 to 72.0

POST_HOC outcome

Timeframe: From randomization until the date of death (assessed up to 32 months).

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=62 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=57 Participants 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.	Arm C: Investigator's Choice n=51 Participants 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 Survival (OS) Time for Patients in Europe + United States With Double-Negative mCRC (EU+US DNmCRC)	8.9 months Interval 6.2 to 12.4	11.9 months Interval 9.7 to 13.8	8.4 months Interval 6.4 to 10.0

POST_HOC outcome

Timeframe: From randomization until the date of death (assessed up to 32 months).

Population: 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.

Outcome measures

Outcome measures
Measure	Arm A: Sym004 (12 mg/kg) n=47 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=46 Participants 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.	Arm C: Investigator's Choice n=38 Participants 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 Survival (OS) Time for Patients in Europe + United States With Triple-Negative mCRC (EU+US TNmCRC)	10.6 months Interval 6.8 to 13.1	12.8 months Interval 9.7 to 14.7	7.3 months Interval 6.3 to 8.8

Adverse Events

Arm A: Sym004 (12 mg/kg)

Serious events: 27 serious events

Other events: 83 other events

Deaths: 68 deaths

Arm B: Sym004 (9/6 mg/kg)

Serious events: 23 serious events

Other events: 84 other events

Deaths: 62 deaths

Arm C: Investigator's Choice

Serious events: 12 serious events

Other events: 67 other events

Deaths: 57 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Scientific Officer

Symphogen A/S

Phone: +45 8838 2600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Arm A: Sym004 (12 mg/kg) n=83 Participants 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.	Arm B: Sym004 (9/6 mg/kg) n=86 Participants 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.	Arm C: Investigator's Choice n=85 Participants 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.
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Global Health Status (Week 1 Day 1)	55.5 score on a scale Interval 0.0 to 92.0	59.7 score on a scale Interval 8.0 to 100.0	55.8 score on a scale Interval 8.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Global Health Status (Week 7 Day 1)	57.4 score on a scale Interval 25.0 to 100.0	59.4 score on a scale Interval 17.0 to 100.0	59.7 score on a scale Interval 17.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Physical Functioning (Week 1 Day 1)	76.4 score on a scale Interval 7.0 to 100.0	78.7 score on a scale Interval 27.0 to 100.0	77.7 score on a scale Interval 27.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Physical Functioning (Week 7 Day 1)	82.1 score on a scale Interval 13.0 to 100.0	83.0 score on a scale Interval 47.0 to 100.0	76.7 score on a scale Interval 40.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Role Functioning (Week 1 Day 1)	75.0 score on a scale Interval 0.0 to 100.0	76.4 score on a scale Interval 0.0 to 100.0	72.5 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Role Functioning (Week 7 Day 1)	81.1 score on a scale Interval 33.0 to 100.0	82.4 score on a scale Interval 50.0 to 100.0	72.8 score on a scale Interval 17.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Emotional Functioning (Week 1 Day 1)	76.6 score on a scale Interval 17.0 to 100.0	77.8 score on a scale Interval 17.0 to 100.0	73.2 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Emotional Functioning (Week 7 Day 1)	74.8 score on a scale Interval 0.0 to 100.0	82.7 score on a scale Interval 33.0 to 100.0	75.3 score on a scale Interval 17.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Cognitive Functioning (Week 1 Day 1)	87.4 score on a scale Interval 33.0 to 100.0	86.2 score on a scale Interval 17.0 to 100.0	87.5 score on a scale Interval 50.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Cognitive Functioning (Week 7 Day 1)	88.1 score on a scale Interval 33.0 to 100.0	88.5 score on a scale Interval 33.0 to 100.0	87.0 score on a scale Interval 33.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Social Functioning (Week 1 Day 1)	78.2 score on a scale Interval 17.0 to 100.0	80.2 score on a scale Interval 17.0 to 100.0	75.4 score on a scale Interval 17.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Fatigue Symptoms (Week 1 Day 1)	35.3 score on a scale Interval 0.0 to 89.0	32.2 score on a scale Interval 0.0 to 100.0	34.7 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Fatigue Symptoms (Week 7 Day 1)	26.3 score on a scale Interval 0.0 to 78.0	25.3 score on a scale Interval 0.0 to 78.0	33.2 score on a scale Interval 0.0 to 78.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Nausea & Vomiting Symptoms (Week 1 Day 1)	7.9 score on a scale Interval 0.0 to 67.0	6.4 score on a scale Interval 0.0 to 100.0	7.8 score on a scale Interval 0.0 to 83.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Nausea & Vomiting Symptoms (Week 7 Day 1)	5.6 score on a scale Interval 0.0 to 33.0	5.1 score on a scale Interval 0.0 to 50.0	8.4 score on a scale Interval 0.0 to 50.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Pain Symptoms (Week 1 Day 1)	27.2 score on a scale Interval 0.0 to 100.0	23.6 score on a scale Interval 0.0 to 100.0	27.8 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Pain Symptoms (Week 7 Day 1)	12.7 score on a scale Interval 0.0 to 50.0	14.6 score on a scale Interval 0.0 to 67.0	24.1 score on a scale Interval 0.0 to 83.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Dyspnoea Symptoms (Week 1 Day 1)	15.9 score on a scale Interval 0.0 to 100.0	17.2 score on a scale Interval 0.0 to 100.0	16.4 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Dyspnoea Symptoms (Week 7 Day 1)	10.4 score on a scale Interval 0.0 to 67.0	8.8 score on a scale Interval 0.0 to 100.0	15.7 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Insomnia Symptoms (Week 1 Day 1)	29.3 score on a scale Interval 0.0 to 100.0	19.1 score on a scale Interval 0.0 to 100.0	21.7 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Insomnia Symptoms (Week 7 Day 1)	27.4 score on a scale Interval 0.0 to 100.0	16.9 score on a scale Interval 0.0 to 100.0	16.6 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Appetite Loss Symptoms (Week 1 Day 1)	22.3 score on a scale Interval 0.0 to 100.0	17.6 score on a scale Interval 0.0 to 100.0	22.2 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Appetite Loss Symptoms (Week 7 Day 1)	16.9 score on a scale Interval 0.0 to 100.0	17.5 score on a scale Interval 0.0 to 67.0	23.0 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Constipation Symptoms (Week 1 Day 1)	15.0 score on a scale Interval 0.0 to 67.0	16.0 score on a scale Interval 0.0 to 100.0	11.4 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Constipation Symptoms (Week 7 Day 1)	11.5 score on a scale Interval 0.0 to 67.0	8.3 score on a scale Interval 0.0 to 67.0	11.1 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Diarrhoea Symptoms (Week 1 Day 1)	12.5 score on a scale Interval 0.0 to 100.0	8.5 score on a scale Interval 0.0 to 100.0	15.9 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Diarrhoea Symptoms (Week 7 Day 1)	8.8 score on a scale Interval 0.0 to 100.0	11.1 score on a scale Interval 0.0 to 67.0	11.0 score on a scale Interval 0.0 to 67.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Financial Difficulties (Week 1 Day 1)	19.7 score on a scale Interval 0.0 to 67.0	16.6 score on a scale Interval 0.0 to 100.0	23.3 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Financial Difficulties (Week 7 Day 1)	19.4 score on a scale Interval 0.0 to 100.0	15.2 score on a scale Interval 0.0 to 67.0	19.3 score on a scale Interval 0.0 to 100.0
Quality of Life Assessed by the EORTC QLQ-C30 (Version 3) Social Functioning (Week 7 Day 1)	77.9 score on a scale Interval 0.0 to 100.0	83.4 score on a scale Interval 50.0 to 100.0	72.7 score on a scale Interval 0.0 to 100.0