Trial Outcomes & Findings for Japanese Phase 1 Trial of Sym004 in Solid Tumors (NCT NCT01955473)

NCT ID: NCT01955473

Last Updated: 2017-08-23

Results Overview

DLT: any of the following National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Grade 4 hematologic or Grade 3/4 non-hematologic toxicities that occurred during DLT observation period of Part A, and were considered by Investigator to be at least possibly related to study treatment, and confirmed by Safety Monitoring Committee. Hematological toxicities: Grade 4 neutropenia, febrile neutropenia, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with bleeding episodes. Nonhematological toxicities: Grade 3 or higher non-hematological toxicity with exception of Grade 3 fatigue/skin toxicity; Grade 3 nausea/vomiting without appropriate prophylactic therapy; Grade 3 diarrhoea recovered within 2 days with adequate treatment or did not accompany fever/dehydration; Grade 3 or 4 laboratory liver parameter abnormalities with duration of less than 3 days.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

51 participants

Primary outcome timeframe

Week 1 up to Week 4 (Part A)

Results posted on

2017-08-23

Participant Flow

First/Last subject (informed consent): 30 October 2013/10 Jun 2015. Study completion date: 30 October 2015. Clinical data cut-off: 30 October 2015. The study was conducted by 6 Investigators in 6 sites in Japan.

A total of 60 subjects were screened for eligibility, out of which and 51 subjects were randomized into the study.

Participant milestones

Participant milestones
Measure	Part A: Sym004 6 mg/kg Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Overall Study STARTED	3	6	6	6	30
Overall Study COMPLETED	3	6	6	6	30
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Japanese Phase 1 Trial of Sym004 in Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=30 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Total n=51 Participants Total of all reporting groups
Age, Continuous	59.7 years STANDARD_DEVIATION 3.51 • n=5 Participants	62.5 years STANDARD_DEVIATION 5.09 • n=7 Participants	66.5 years STANDARD_DEVIATION 5.96 • n=5 Participants	59.0 years STANDARD_DEVIATION 9.32 • n=4 Participants	61.2 years STANDARD_DEVIATION 7.20 • n=21 Participants	61.6 years STANDARD_DEVIATION 7.03 • n=10 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	6 Participants n=21 Participants	12 Participants n=10 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	24 Participants n=21 Participants	39 Participants n=10 Participants

PRIMARY outcome

Timeframe: Week 1 up to Week 4 (Part A)

Population: DLT Analysis Set consisted of all subjects who received at least 3 of 4 weekly administrations (for weekly dosing cohort) or who received 2 biweekly administrations (for biweekly dosing cohort) and experienced a DLT during DLT observation period.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Number of Subjects With Dose Limiting Toxicities (DLTs) Determined in Part-A	0 subjects	0 subjects	0 subjects	0 subjects	—

PRIMARY outcome

Timeframe: Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks

Population: Safety analysis set consisted of all subjects (from Parts A and B) who received at least 1 administration of Sym004.

An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. AEs were considered treatment emergent if they started on or after the day of first administration of the Sym004 or if they started prior to administration but worsened after receiving the first dose of treatment.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=30 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death TEAEs	3 subjects	6 subjects	6 subjects	6 subjects	30 subjects
Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death Serious TEAEs	0 subjects	0 subjects	2 subjects	0 subjects	9 subjects
Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death TEAE leading to Discontinuation	0 subjects	0 subjects	0 subjects	0 subjects	4 subjects
Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death TEAEs Leading to Death	0 subjects	0 subjects	0 subjects	0 subjects	3 subjects

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, 48 and 168 hours post-infusion at Week 1

Population: The Pharmacokinetics (PK) Analysis Set consisted of all subjects (from Parts A and B) who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=7 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) at Week 1: Single Dose mAb992	3685.5 μg*h/mL Geometric Coefficient of Variation 38.1	5893.1 μg*h/mL Geometric Coefficient of Variation 33.3	8957.3 μg*h/mL Geometric Coefficient of Variation 29.3	12783 μg*h/mL Geometric Coefficient of Variation 26.0	7073.5 μg*h/mL Geometric Coefficient of Variation 15.1
Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) at Week 1: Single Dose mAb1024	4109.0 μg*h/mL Geometric Coefficient of Variation 25.6	6572.1 μg*h/mL Geometric Coefficient of Variation 30.5	10213 μg*h/mL Geometric Coefficient of Variation 24.1	15917 μg*h/mL Geometric Coefficient of Variation 30.6	10336 μg*h/mL Geometric Coefficient of Variation 27.4

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, and 168 hours post-infusion at Week 4

Population: The PK Analysis Set consisted of all subjects (from Parts A and B) who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here "Number of Participants Analyzed" =subjects who were evaluable for this outcome and "n" =subjects who were evaluable for specified monoclonal antibody.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=2 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=5 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=5 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) for the Weekly Regimen at Week 4: Multiple Dose mAb992 (n=2, 5, 6, 5)	NA μg*h/mL Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	7111.1 μg*h/mL Geometric Coefficient of Variation 41.7	15298 μg*h/mL Geometric Coefficient of Variation 41.4	13053 μg*h/mL Geometric Coefficient of Variation 18.7	—
Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) for the Weekly Regimen at Week 4: Multiple Dose mAb1024 (n=2, 4, 6, 5)	NA μg*h/mL Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	9738.5 μg*h/mL Geometric Coefficient of Variation 36.8	21422 μg*h/mL Geometric Coefficient of Variation 45.5	22016 μg*h/mL Geometric Coefficient of Variation 32.2	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, 48 and 168 hours post-infusion at Week 1

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=7 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) at Week 1: Single Dose mAb992	22.50 μg*h/mL/mg Geometric Coefficient of Variation 29.5	23.24 μg*h/mL/mg Geometric Coefficient of Variation 30.7	25.79 μg*h/mL/mg Geometric Coefficient of Variation 18.0	21.69 μg*h/mL/mg Geometric Coefficient of Variation 24.8	22.70 μg*h/mL/mg Geometric Coefficient of Variation 17.5
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) at Week 1: Single Dose mAb1024	25.09 μg*h/mL/mg Geometric Coefficient of Variation 20.1	25.91 μg*h/mL/mg Geometric Coefficient of Variation 27.7	29.41 μg*h/mL/mg Geometric Coefficient of Variation 11.1	27.01 μg*h/mL/mg Geometric Coefficient of Variation 26.0	33.17 μg*h/mL/mg Geometric Coefficient of Variation 27.8

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, and 168 hours post-infusion at Week 4

Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Here dose normalized AUC are presented for both monoclonal antibodies. Dose normalized AUC for AUC0-168 was calculated as AUC(0-168)/Dose. Results were to be assessed for weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) only.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=2 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=5 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=5 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Dose Nornamized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) for the Weekly Regimen at Week 4: Multiple Dose mAb992 (n= 2, 5, 6, 5)	NA μg*h/mL/mg Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	43.90 μg*h/mL/mg Geometric Coefficient of Variation 27.3	43.45 μg*h/mL/mg Geometric Coefficient of Variation 29.3	42.38 μg*h/mL/mg Geometric Coefficient of Variation 15.0	—
Dose Nornamized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) for the Weekly Regimen at Week 4: Multiple Dose mAb1024 (n= 2, 4, 6, 5)	NA μg*h/mL/mg Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	59.12 μg*h/mL/mg Geometric Coefficient of Variation 30.6	60.85 μg*h/mL/mg Geometric Coefficient of Variation 32.9	72.36 μg*h/mL/mg Geometric Coefficient of Variation 28.2	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, 48, 168, 336 hours post-infusion at Week 1

Population: The PK Analysis Set consisted of all subjects who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=6 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Area Under Concentration-time Curve (AUC) From Start of First Infusion to 336 Hours (AUC0-336hours) For the Biweekly Regimen at Week 1: Single Dose mAb992	17318 μg*h/mL Geometric Coefficient of Variation 27.0	—	—	—	—
Area Under Concentration-time Curve (AUC) From Start of First Infusion to 336 Hours (AUC0-336hours) For the Biweekly Regimen at Week 1: Single Dose mAb1024	22458 μg*h/mL Geometric Coefficient of Variation 29.7	—	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, 168 and 336 hours post-infusion at Week 5

Population: The PK Analysis Set consisted of all subjects who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here, "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=5 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Area Under Concentration-time Curve (AUC) From Start of First Infusion to 336 Hours (AUC0-336hours) For the Biweekly Regimen at Week 5: Multiple Dose mAb992	24755 μg*h/mL Geometric Coefficient of Variation 31.8	—	—	—	—
Area Under Concentration-time Curve (AUC) From Start of First Infusion to 336 Hours (AUC0-336hours) For the Biweekly Regimen at Week 5: Multiple Dose mAb1024	32336 μg*h/mL Geometric Coefficient of Variation 30.8	—	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, 48, 168, 336 hours post-infusion at Week 1

Population: The PK Analysis Set consisted of all subjects who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004.

Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Here dose normalized AUC are presented for both monoclonal antibodies. Results were to be assessed for biweekly dosing cohort (Part A: Sym004 18 mg/kg) only. Dose normalized AUC for AUC0-336 was calculated as AUC(0-336)/Dose.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=6 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 336 Hours (AUC0-336hours) For the Biweekly Regimen at Week 1: Single Dose mAb992	29.39 μg*h/mL/mg Geometric Coefficient of Variation 27.1	—	—	—	—
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 336 Hours (AUC0-336hours) For the Biweekly Regimen at Week 1: Single Dose mAb1024	38.11 μg*h/mL/mg Geometric Coefficient of Variation 26.9	—	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, 168 and 336 hours post-infusion at Week 5

Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Here dose normalized AUC are presented for both monoclonal antibodies. Results were to be assessed for biweekly dosing cohort (Part A: Sym004 18 mg/kg) only. Dose normalized AUC for AUC0-336 was calculated as AUC(0-336)/Dose.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=5 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 336 Hours (AUC0-336hours) For the Biweekly Regimen at Week 5: Multiple Dose mAb992	42.45 μg*h/mL/mg Geometric Coefficient of Variation 29.9	—	—	—	—
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 336 Hours (AUC0-336hours) For the Biweekly Regimen at Week 5: Multiple Dose mAb1024	55.46 μg*h/mL/mg Geometric Coefficient of Variation 25.7	—	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, and 48 hours post-infusion at Week 1

Population: The PK Analysis Set consisted of all subjects who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=6 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 1: Single Dose mAb992	19896 μg*h/mL Geometric Coefficient of Variation 28.9	—	—	—	—
Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 1: Single Dose mAb1024	27554 μg*h/mL Geometric Coefficient of Variation 30.7	—	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12 and 24 hours post-infusion at Week 5

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=5 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 5: Multiple Dose mAb992	30127 μg*h/mL Geometric Coefficient of Variation 36.6	—	—	—	—
Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 5: Multiple Dose mAb1024	43308 μg*h/mL Geometric Coefficient of Variation 37.8	—	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, and 48 hours post-infusion at Week 1

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=7 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) at Week 1: Single Dose mAb992 (3, 6, 6, 6, 7)	27.30 μg*h/mL/mg Geometric Coefficient of Variation 26.7	30.33 μg*h/mL/mg Geometric Coefficient of Variation 37.7	34.471 μg*h/mL/mg Geometric Coefficient of Variation 22.5	33.77 μg*h/mL/mg Geometric Coefficient of Variation 30.3	31.05 μg*h/mL/mg Geometric Coefficient of Variation 24.6
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) at Week 1: Single Dose mAb1024 (3, 6, 6, 6, 6)	31.86 μg*h/mL/mg Geometric Coefficient of Variation 21.9	36.20 μg*h/mL/mg Geometric Coefficient of Variation 37.4	43.41 μg*h/mL/mg Geometric Coefficient of Variation 23.1	46.77 μg*h/mL/mg Geometric Coefficient of Variation 30.9	47.48 μg*h/mL/mg Geometric Coefficient of Variation 17.5

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Here dose normalized AUC are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were only applicable for Week 4 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was not applicable for Week 4 assessment. Dose normalized AUC for AUC0-inf was calculated as AUC(0-inf)/Dose.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=2 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=5 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=5 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) for the Weekly Regimen at Week 4: Multiple Dose mAb992 (n= 1, 5, 6, 5)	NA μg*h/mL/mg Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	59.65 μg*h/mL/mg Geometric Coefficient of Variation 37.3	77.86 μg*h/mL/mg Geometric Coefficient of Variation 65.2	72.22 μg*h/mL/mg Geometric Coefficient of Variation 17.1	—
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) for the Weekly Regimen at Week 4: Multiple Dose mAb1024 (n= 2, 4, 6, 4)	NA μg*h/mL/mg Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	94.91 μg*h/mL/mg Geometric Coefficient of Variation 44.7	118.1 μg*h/mL/mg Geometric Coefficient of Variation 57.5	136.9 μg*h/mL/mg Geometric Coefficient of Variation 46.8	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Population: The PK Analysis Set consisted of all subjects who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Here dose normalized AUC are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were not applicable for Week 5 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was only applicable for Week 5 assessment. Dose normalized AUC for AUC0-inf was calculated as AUC(0-inf)/Dose.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=5 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 5: Multiple Dose mAb992	51.67 μg*h/mL/mg Geometric Coefficient of Variation 36.2	—	—	—	—
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 5: Multiple Dose mAb1024	74.28 μg*h/mL/mg Geometric Coefficient of Variation 36.3	—	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=7 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Terminal Half-life (t1/2) of Sym004 at Week 1: Single Dose mAb992 (n= 3,6,6,6,7)	66.478 hours Geometric Coefficient of Variation 10.0	79.041 hours Geometric Coefficient of Variation 18.8	82.865 hours Geometric Coefficient of Variation 21.1	111.69 hours Geometric Coefficient of Variation 18.9	87.257 hours Geometric Coefficient of Variation 21.1
Terminal Half-life (t1/2) of Sym004 at Week 1: Single Dose mAb1024 (n= 3,6,6,6,6)	74.075 hours Geometric Coefficient of Variation 8.8	91.303 hours Geometric Coefficient of Variation 21.7	100.05 hours Geometric Coefficient of Variation 24.3	134.48 hours Geometric Coefficient of Variation 27.8	100.57 hours Geometric Coefficient of Variation 34.8

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination. Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Terminal t1/2 are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were only applicable for Week 4 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was not applicable for Week 4 assessment.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=2 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=5 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=5 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Terminal Half-life (t1/2) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose mAb992 (n= 1, 5, 6, 5)	NA hours Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	85.228 hours Geometric Coefficient of Variation 24.4	135.98 hours Geometric Coefficient of Variation 52.5	132.14 hours Geometric Coefficient of Variation 13.9	—
Terminal Half-life (t1/2) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose mAb1024 (n= 2, 4, 6, 4)	NA hours Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	117.8 hours Geometric Coefficient of Variation 27.5	155.9 hours Geometric Coefficient of Variation 37.4	163.8 hours Geometric Coefficient of Variation 27.5	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Population: The PK Analysis Set consisted of all subjects who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination. Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Terminal t1/2 are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were not applicable for Week 5 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was only applicable for Week 5 assessment.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=5 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Terminal Half-life (t1/2) of Sym004 For the Biweekly Regimen at Week 5: Multiple Dose mAb992	130.39 hours Geometric Coefficient of Variation 26.4	—	—	—	—
Terminal Half-life (t1/2) of Sym004 For the Biweekly Regimen at Week 5: Multiple Dose mAb1024	163.6 hours Geometric Coefficient of Variation 36.3	—	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1

Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). CL are presented for both monoclonal antibodies.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=7 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Clearance (CL) of Sym004 at Week 1: Single Dose mAb992 (n= 3,6,6,6,7)	0.036626 Liter/hour Geometric Coefficient of Variation 26.7	0.032967 Liter/hour Geometric Coefficient of Variation 37.7	0.029012 Liter/hour Geometric Coefficient of Variation 22.5	0.029615 Liter/hour Geometric Coefficient of Variation 30.3	0.032202 Liter/hour Geometric Coefficient of Variation 24.6
Clearance (CL) of Sym004 at Week 1: Single Dose mAb1024 (n= 3,6,6,6,6)	0.031385 Liter/hour Geometric Coefficient of Variation 21.9	0.027622 Liter/hour Geometric Coefficient of Variation 37.4	0.023033 Liter/hour Geometric Coefficient of Variation 23.1	0.021383 Liter/hour Geometric Coefficient of Variation 30.9	0.021058 Liter/hour Geometric Coefficient of Variation 17.6

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Clearance at steady state was reported. Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). CLss are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were only applicable for Week 4 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was not applicable for Week 4 assessment.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=2 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=5 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=5 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Clearance at Steady-state (CLss) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose mAb992 (n= 2, 5, 6, 5)	NA Liter/hour Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	0.022778 Liter/hour Geometric Coefficient of Variation 27.3	0.023015 Liter/hour Geometric Coefficient of Variation 29.3	0.023589 Liter/hour Geometric Coefficient of Variation 15.0	—
Clearance at Steady-state (CLss) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose mAb1024 (n= 2, 4, 6, 4)	NA Liter/hour Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	0.017 Liter/hour Geometric Coefficient of Variation 30.6	0.016 Liter/hour Geometric Coefficient of Variation 32.9	0.014 Liter/hour Geometric Coefficient of Variation 28.2	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Population: The PK Analysis Set consisted of all subjects who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Clearance at steady state was reported. Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). CLss are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were not applicable for Week 5 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was only applicable for Week 5 assessment.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=5 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Clearance at Steady-state (CLss) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose mAb992	0.023552 Liter/hour Geometric Coefficient of Variation 29.9	—	—	—	—
Clearance at Steady-state (CLss) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose mAb1024	0.018 Liter/hour Geometric Coefficient of Variation 25.6	—	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=7 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Volume of Distribution at the Elimination Phase (Vz) of Sym004 at Week 1: Single Dose mAb992 (n= 3,6,6,6,7)	3.5130 Liter Geometric Coefficient of Variation 36.1	3.7593 Liter Geometric Coefficient of Variation 21.9	3.4688 Liter Geometric Coefficient of Variation 17.8	4.7726 Liter Geometric Coefficient of Variation 23.3	4.0536 Liter Geometric Coefficient of Variation 10.8
Volume of Distribution at the Elimination Phase (Vz) of Sym004 at Week 1: Single Dose mAb1024 (n= 3,6,6,6,6)	3.3543 Liter Geometric Coefficient of Variation 16.7	3.6384 Liter Geometric Coefficient of Variation 17.6	3.3245 Liter Geometric Coefficient of Variation 3.4	4.1483 Liter Geometric Coefficient of Variation 29.1	3.0558 Liter Geometric Coefficient of Variation 47.0

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Volume of distribution was defined as the theoretical volume in which the total amount of drug needed to be uniformly distributed to produce the desired serum concentration of a drug. Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Vss are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were only applicable for Week 4 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was not applicable for Week 4 assessment.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=2 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=5 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=5 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Volume of Distribution at Steady State (Vss) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose mAb992 (n= 1, 5, 6, 5)	NA Liter Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	2.7931 Liter Geometric Coefficient of Variation 15.4	4.4777 Liter Geometric Coefficient of Variation 26.2	4.4383 Liter Geometric Coefficient of Variation 17.9	—
Volume of Distribution at Steady State (Vss) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose mAb1024 (n= 2, 4, 6, 4)	NA Liter Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	2.85 Liter Geometric Coefficient of Variation 20.6	3.71 Liter Geometric Coefficient of Variation 21.3	3.40 Liter Geometric Coefficient of Variation 24.9	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Population: The PK Analysis Set consisted of all subjects who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Volume of distribution was defined as the theoretical volume in which the total amount of drug needed to be uniformly distributed to produce the desired serum concentration of a drug. Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Vss are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were not applicable for Week 5 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was only applicable for Week 5 assessment.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=5 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Volume of Distribution at Steady State (Vss) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose mAb992	4.3988 Liter Geometric Coefficient of Variation 24.4	—	—	—	—
Volume of Distribution at Steady State (Vss) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose mAb1024	4.20 Liter Geometric Coefficient of Variation 27.7	—	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1

Population: The PK Analysis Set consisted of all subjects (from Parts A and B) who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=7 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Maximum Serum Concentration (Cmax) of Sym004 at Week 1: Single Dose mAb992	50.131 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 29.2	85.088 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 25.3	120.37 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 33.6	157.71 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 18.6	88.589 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 15.0
Maximum Serum Concentration (Cmax) of Sym004 at Week 1: Single Dose mAb1024	54.660 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 15.6	89.443 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 26.2	116.18 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 31.2	187.03 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 23.9	146.92 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 56.3

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Population: The PK Analysis Set consisted of all subjects (from Parts A and B) who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Cmax are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were only applicable for Week 4 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was not applicable for Week 4 assessment.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Maximum Serum Concentration (Cmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose mAb992	76.094 μg/mL Geometric Coefficient of Variation 16.4	86.763 μg/mL Geometric Coefficient of Variation 34.0	181.62 μg/mL Geometric Coefficient of Variation 31.6	143.79 μg/mL Geometric Coefficient of Variation 23.4	—
Maximum Serum Concentration (Cmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose mAb1024	89.26 μg/mL Geometric Coefficient of Variation 10.2	91.70 μg/mL Geometric Coefficient of Variation 33.4	221.3 μg/mL Geometric Coefficient of Variation 21.1	231.9 μg/mL Geometric Coefficient of Variation 32.8	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Population: The PK Analysis Set consisted of all subjects who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004.

Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Cmax are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were not applicable for Week 5 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was only applicable for Week 5 assessment.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=6 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Maximum Serum Concentration (Cmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose mAb992	187.40 μg/mL Geometric Coefficient of Variation 24.3	—	—	—	—
Maximum Serum Concentration (Cmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose mAb1024	224.0 μg/mL Geometric Coefficient of Variation 24.7	—	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1

Population: The PK Analysis Set consisted of all subjects (from Parts A and B) who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=7 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Dose Normalized Maximum Serum Concentration (Cmax) of Sym004 at Week 1: Single Dose mAb1024	0.334 μg/mL/mg Geometric Coefficient of Variation 8.4	0.353 μg/mL/mg Geometric Coefficient of Variation 26.0	0.334 μg/mL/mg Geometric Coefficient of Variation 13.4	0.317 μg/mL/mg Geometric Coefficient of Variation 15.6	0.471 μg/mL/mg Geometric Coefficient of Variation 58.7
Dose Normalized Maximum Serum Concentration (Cmax) of Sym004 at Week 1: Single Dose mAb992	0.306 μg/mL/mg Geometric Coefficient of Variation 19.8	0.336 μg/mL/mg Geometric Coefficient of Variation 23.5	0.346 μg/mL/mg Geometric Coefficient of Variation 22.0	0.268 μg/mL/mg Geometric Coefficient of Variation 19.1	0.284 μg/mL/mg Geometric Coefficient of Variation 13.0

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Population: The PK Analysis Set consisted of all subjects (from Parts A and B) who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Here dose normalized Cmax are presented for both monoclonal antibodies. Dose normalized Cmax was calculated as Cmax/Dose. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were only applicable for Week 4 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was not applicable for Week 4 assessment.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Dose Nornamized Maximum Serum Concentration (Cmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose mAb992	0.486 μg/mL/mg Geometric Coefficient of Variation 4.4	0.524 μg/mL/mg Geometric Coefficient of Variation 31.4	0.516 μg/mL/mg Geometric Coefficient of Variation 18.4	0.466 μg/mL/mg Geometric Coefficient of Variation 12.8	—
Dose Nornamized Maximum Serum Concentration (Cmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose mAb1024	0.570 μg/mL/mg Geometric Coefficient of Variation 7.1	0.553 μg/mL/mg Geometric Coefficient of Variation 32.3	0.629 μg/mL/mg Geometric Coefficient of Variation 12.9	0.752 μg/mL/mg Geometric Coefficient of Variation 24.3	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Population: The PK Analysis Set consisted of all subjects who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004.

Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Here dose normalized Cmax are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were not applicable for Week 5 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was only applicable for Week 5 assessment. Dose normalized Cmax was calculated as Cmax/Dose.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=6 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Dose Normalized Maximum Serum Concentration (Cmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose mAb992	0.318 μg/mL/mg Geometric Coefficient of Variation 25.0	—	—	—	—
Dose Normalized Maximum Serum Concentration (Cmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose mAb1024	0.380 μg/mL/mg Geometric Coefficient of Variation 20.2	—	—	—	—

SECONDARY outcome

Timeframe: Pre-infusion at Week 2, 3, 5, 6, 7, 8, End of Trial (up to 41.1 weeks) and Follow up (up to 45.1 Weeks)

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=29 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Trough Concentrations (Ctrough) of Sym004 mAb992 Week 2 pre-dose (n= 3, 6, 6, 6, 29)	8.38333 μg/mL Standard Deviation 2.562935	16.3617 μg/mL Standard Deviation 7.384964	29.4483 μg/mL Standard Deviation 9.716758	45.1117 μg/mL Standard Deviation 17.24716	20.1517 μg/mL Standard Deviation 8.411459
Trough Concentrations (Ctrough) of Sym004 mAb992 Week 3 pre-dose (n= 3, 6, 5, 6, 26)	19.8700 μg/mL Standard Deviation 9.570564	16.7033 μg/mL Standard Deviation 8.283479	57.7280 μg/mL Standard Deviation 29.34743	15.3600 μg/mL Standard Deviation 6.817337	32.6969 μg/mL Standard Deviation 12.62782
Trough Concentrations (Ctrough) of Sym004 mAb992 Week 5 pre-dose (n= 2, 5, 6, 0, 23)	NA μg/mL Standard Deviation NA Mean and standard deviation were not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	22.9260 μg/mL Standard Deviation 11.37231	66.0267 μg/mL Standard Deviation 37.84088	NA μg/mL Standard Deviation NA No subjects were evaluable hence the parameter at specified time point was not analyzed.	71.0739 μg/mL Standard Deviation 67.33365
Trough Concentrations (Ctrough) of Sym004 mAb992 Week 6 pre-dose (n= 3, 5, 5, 4, 21)	25.5833 μg/mL Standard Deviation 21.14422	26.3340 μg/mL Standard Deviation 13.43829	92.4920 μg/mL Standard Deviation 47.20264	64.3750 μg/mL Standard Deviation 20.56197	53.2224 μg/mL Standard Deviation 30.76489
Trough Concentrations (Ctrough) of Sym004 mAb992 Week 7 pre-dose (n= 2, 4, 4, 4, 21)	NA μg/mL Standard Deviation NA Mean and standard deviation were not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	25.7500 μg/mL Standard Deviation 16.36742	70.9875 μg/mL Standard Deviation 61.05280	36.1700 μg/mL Standard Deviation 7.608184	66.1524 μg/mL Standard Deviation 65.22446
Trough Concentrations (Ctrough) of Sym004 mAb992 Week 8 pre-dose (n= 2, 4, 3, 2, 12)	NA μg/mL Standard Deviation NA Mean and standard deviation were not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	24.8650 μg/mL Standard Deviation 13.70631	122.283 μg/mL Standard Deviation 79.73053	NA μg/mL Standard Deviation NA Mean and standard deviation were not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	60.4542 μg/mL Standard Deviation 25.37663
Trough Concentrations (Ctrough) of Sym004 mAb992 End of Trial(up to 41.1weeks)(n=3,6,6,6,27)	NA μg/mL Standard Deviation NA Data could not be estimated as it was below lower limit of quantitation (LLOQ) for mAb992 (LLOQ: 0.5 μg/mL)	NA μg/mL Standard Deviation NA Data could not be estimated as it was below lower limit of quantitation (LLOQ) for mAb992 (LLOQ: 0.5 μg/mL)	13.8400 μg/mL Standard Deviation 32.25929	1.24833 μg/mL Standard Deviation 2.197339	5.63333 μg/mL Standard Deviation 11.64986
Trough Concentrations (Ctrough) of Sym004 mAb992 Follow up (up to 45.1 Weeks)(n=1,2,3,4,19)	NA μg/mL Standard Deviation NA Mean and standard deviation were not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	NA μg/mL Standard Deviation NA Mean and standard deviation were not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	NA μg/mL Standard Deviation NA Data could not be estimated as it was below lower limit of quantitation (LLOQ) for mAb992 (LLOQ: 0.5 μg/mL)	NA μg/mL Standard Deviation NA Data could not be estimated as it was below lower limit of quantitation (LLOQ) for mAb992 (LLOQ: 0.5 μg/mL)	NA μg/mL Standard Deviation NA Data could not be estimated as it was below lower limit of quantitation (LLOQ) for mAb992 (LLOQ: 0.5 μg/mL)
Trough Concentrations (Ctrough) of Sym004 mAb1024 Week 2 pre-dose (n= 3, 6, 6, 6, 29)	10.6767 μg/mL Standard Deviation 2.688128	20.2433 μg/mL Standard Deviation 8.704451	38.7017 μg/mL Standard Deviation 12.01645	58.6967 μg/mL Standard Deviation 17.29509	27.8641 μg/mL Standard Deviation 12.33288
Trough Concentrations (Ctrough) of Sym004 mAb1024 Week 3 pre-dose (n= 3, 6, 5, 6, 26)	23.8000 μg/mL Standard Deviation 9.525382	22.7517 μg/mL Standard Deviation 14.69928	69.9460 μg/mL Standard Deviation 21.36079	24.7000 μg/mL Standard Deviation 11.16315	44.6531 μg/mL Standard Deviation 17.91820
Trough Concentrations (Ctrough) of Sym004 mAb1024 Week 5 pre-dose (n= 2, 5, 6, 0, 23)	NA μg/mL Standard Deviation NA Mean and standard deviation were not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	31.8900 μg/mL Standard Deviation 17.43852	98.6550 μg/mL Standard Deviation 46.85021	NA μg/mL Standard Deviation NA No subjects were evaluable hence the parameter at specified time point was not analyzed.	82.6235 μg/mL Standard Deviation 49.01981
Trough Concentrations (Ctrough) of Sym004 mAb1024 Week 6 pre-dose (n= 3, 5, 5, 4, 21)	31.8700 μg/mL Standard Deviation 23.97075	35.2440 μg/mL Standard Deviation 18.90163	128.858 μg/mL Standard Deviation 41.31495	90.9275 μg/mL Standard Deviation 26.82442	80.0024 μg/mL Standard Deviation 35.72029
Trough Concentrations (Ctrough) of Sym004 mAb1024 Week 7 pre-dose (n= 2, 4, 4, 4, 21)	NA μg/mL Standard Deviation NA Mean and standard deviation were not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	36.1125 μg/mL Standard Deviation 24.42487	107.843 μg/mL Standard Deviation 76.48666	54.9275 μg/mL Standard Deviation 13.15679	94.4729 μg/mL Standard Deviation 52.58200
Trough Concentrations (Ctrough) of Sym004 mAb1024 Week 8 pre-dose (n= 2, 4, 3, 2, 12)	NA μg/mL Standard Deviation NA Mean and standard deviation were not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	34.6050 μg/mL Standard Deviation 19.49550	166.207 μg/mL Standard Deviation 52.87010	NA μg/mL Standard Deviation NA Mean and standard deviation were not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	93.0283 μg/mL Standard Deviation 47.35483
Trough Concentrations (Ctrough) of Sym004 mAb1024End of Trial(up to 41.1weeks)(n=3,6,6,6,27)	NA μg/mL Standard Deviation NA Data could not be estimated as it was below lower limit of quantitation (LLOQ) for mAb1024 (LLOQ: 0.5 μg/mL)	NA μg/mL Standard Deviation NA Data could not be estimated as it was below lower limit of quantitation (LLOQ) for mAb1024 (LLOQ: 0.5 μg/mL)	25.4667 μg/mL Standard Deviation 58.32014	3.73333 μg/mL Standard Deviation 6.795639	11.2478 μg/mL Standard Deviation 19.88056
Trough Concentrations (Ctrough) of Sym004 mAb1024 Follow up (up to 45.1 Weeks)(n=1,2,3,4,19)	NA μg/mL Standard Deviation NA Mean and standard deviation were not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	NA μg/mL Standard Deviation NA Mean and standard deviation were not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation	NA μg/mL Standard Deviation NA Data could not be estimated as it was below lower limit of quantitation (LLOQ) for mAb1024 (LLOQ: 0.5 μg/mL)	NA μg/mL Standard Deviation NA Data could not be estimated as it was below lower limit of quantitation (LLOQ) for mAb1024 (LLOQ: 0.5 μg/mL)	NA μg/mL Standard Deviation NA Data could not be estimated as it was below lower limit of quantitation (LLOQ) for mAb1024 (LLOQ: 0.5 μg/mL)

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1

Population: The PK Analysis Set consisted of all subjects (from Parts A and B) who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=7 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Time to Reach Maximum Concentration (Tmax) of Sym004 at Week 1: Single Dose mAb992	2.07 hours Interval 2.0 to 14.0	5.12 hours Interval 3.1 to 7.2	5.73 hours Interval 3.0 to 11.0	7.21 hours Interval 3.2 to 15.0	6.30 hours Interval 3.2 to 11.0
Time to Reach Maximum Concentration (Tmax) of Sym004 at Week 1: Single Dose mAb1024	2.05 hours Interval 2.0 to 2.1	7.20 hours Interval 3.2 to 11.0	6.66 hours Interval 3.1 to 11.0	7.15 hours Interval 3.2 to 7.6	7.13 hours Interval 3.2 to 11.0

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Population: The PK Analysis Set consisted of all subjects (from Parts A and B) who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Tmax are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were only applicable for Week 4 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was not applicable for Week 4 assessment.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Time to Reach Maximum Concentration (Tmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose mAb992	10.1 hours Interval 6.0 to 14.0	5.94 hours Interval 2.325 to 9.0	9.13 hours Interval 7.1 to 11.0	5.13 hours Interval 2.9 to 11.0	—
Time to Reach Maximum Concentration (Tmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose mAb1024	2.07 hours Interval 2.0 to 2.1	6.13 hours Interval 2.0 to 18.0	5.18 hours Interval 3.0 to 7.3	7.10 hours Interval 3.1 to 11.0	—

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Population: The PK Analysis Set consisted of all subjects who received at least 1 administration of Sym004 and who provided sufficient data for a concentration time profile for Sym004.

Sym004 is a mixture of two mouse-human chimeric immunoglobulin G1 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (called monoclonal antibodies \[mAb\] 992 and mAb 1024). Tmax are presented for both monoclonal antibodies. Weekly dosing cohorts (Part A: Sym004 6 mg/kg, Part A: Sym004 9/6 mg/kg, Part A: Sym004 12 mg/kg, Part B: Sym004 12 mg/kg) were not applicable for Week 5 assessment. Biweekly dosing cohort (Part A: Sym004 18 mg/kg) was only applicable for Week 5 assessment.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=6 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Time to Reach Maximum Concentration (Tmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose mAb992	7.03 hours Interval 3.1 to 11.0	—	—	—	—
Time to Reach Maximum Concentration (Tmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose mAb1024	5.28 hours Interval 3.1 to 11.0	—	—	—	—

SECONDARY outcome

Timeframe: Week 7 and thereafter every 6 weeks, up to 4 weeks after last dose for Part A or up to 8 weeks after the last dose for Part B (up to 45.1 Weeks)

Population: Efficacy Analysis Set consisted of all subjects (from Parts A and B) who received at least 1 administration of Sym004 and who had baseline tumor assessment and at least 1 tumor assessment according to RECISTv1.1 after first dose of trial medication.

Percentage of subjects with best overall response (defined as confirmed CR or PR) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) was reported. CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimiter (mm). PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Confirmed CR or PR was defined as the response that was confirmed at an interval of at least 4 weeks.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=30 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Percentage of Subjects With Best Overall Response CR	0 percentage of subjects	0 percentage of subjects	0 percentage of subjects	0 percentage of subjects	0 percentage of subjects
Percentage of Subjects With Best Overall Response PR	0 percentage of subjects	0 percentage of subjects	33.3 percentage of subjects	0 percentage of subjects	16.7 percentage of subjects

SECONDARY outcome

Timeframe: Week 7 and thereafter every 6 weeks until the first date of objectively documented recurrent or progressive disease, up to 45.1 Weeks

The duration of overall response was measured from the time measurement criteria were first met for CR or PR (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented. CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Confirmed CR or PR was defined as the response that was confirmed at an interval of at least 4 weeks.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=2 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=5 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Duration of Overall Response	—	—	25.85 Weeks Interval 24.6 to 27.1	—	10.40 Weeks Interval 8.1 to 22.1

SECONDARY outcome

Timeframe: Week 7 and thereafter every 6 weeks, up to 4 weeks after last dose for Part A or up to 8 weeks after the last dose for Part B (up to 45.1 Weeks)

Percentage of subjects with disease control (defined as confirmed CR, confirmed PR, or confirmed SD) ) according to RECIST Version 1.1 was reported. CR: disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Confirmed CR or PR: response confirmed at an interval of at least 4 weeks. Confirmed SD: response confirmed at an interval of at least 6 weeks.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=30 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Percentage of Subjects With Disease Control	66.7 percentage of subjects Interval 9.4 to 99.2	66.7 percentage of subjects Interval 22.3 to 95.7	50.0 percentage of subjects Interval 11.8 to 88.2	16.7 percentage of subjects Interval 0.4 to 64.1	56.7 percentage of subjects Interval 37.4 to 74.5

SECONDARY outcome

Timeframe: Week 7 and thereafter every 6 weeks until the first date of objectively documented recurrent or progressive disease, up to 45.1 weeks

Duration of disease control measured from the time measurement criteria were first met for CR, PR, or SD (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented. CR: disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=2 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=4 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=3 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=1 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=17 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Duration of Disease Control	6.10 Weeks Interval 6.1 to 6.1	5.35 Weeks Interval 4.0 to 6.1	24.60 Weeks Interval 4.1 to 27.1	6.10 Weeks Interval 6.1 to 6.1	5.90 Weeks Interval 0.1 to 22.1

SECONDARY outcome

Timeframe: Time from enrollment until the date of objectively documented disease progression or death, up to 45.1 Weeks

Time to progression was defined as the time from date of subject enrollment until the date that disease progression was objectively documented. TTP estimated using the Kaplan-Meier estimates. TTP was planned to be reported for Part B alone and Part A/B combined reporting arms.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=30 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=51 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Time to Progression	2.37 months Interval 1.38 to 3.68	2.33 months Interval 1.41 to 2.79	—	—	—

SECONDARY outcome

Timeframe: Time from enrollment until the date of objectively documented disease progression or death, up to 45.1 Weeks

The Progression-free survival time was measured from the date of subject enrollment until the date that disease progression was objectively documented or death. Progression-free survival time estimated with using the Kaplan-Meier method. Progression-free survival time was planned to be reported for Part B alone and Part A/B combined reporting arms.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=30 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=51 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Progression-free Survival Time	2.12 months Interval 1.38 to 2.83	2.30 months Interval 1.41 to 2.79	—	—	—

SECONDARY outcome

Timeframe: Week 1 (pre-dose) up to Follow-up assessment (up to maximum 45.1 Weeks)

Population: Anti-drug Antibody (ADA) titer could not be estimated because there were no subjects who were confirmed to have ADA positive test results during the confirmatory analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1 (pre-dose), Week 4 and Week 5

Population: The Biomarker analysis set consisted of all subjects who received at least 1 administration of Sym004 and who had at least 1 biomarker evaluation.

IHC is a staining process performed on fresh/frozen cancer tissue. IHC is used to show whether or not the cancer cells have Human Epidermal Growth Receptor (HER2) and/or hormone receptors on their surface. A value designated the IHC score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=13 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 1: 0 Score	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	7.7 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 1: greater than (>) 0-less than(<) 100 Score	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 1: 100 - <200 Score	33.3 percentage of subjects	0.0 percentage of subjects	16.7 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 1: 200 - 300 Score	66.7 percentage of subjects	83.3 percentage of subjects	83.3 percentage of subjects	100.0 percentage of subjects	76.9 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 1: Missing	0.0 percentage of subjects	16.7 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	15.4 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 4: 0 Score	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 4: >0 - <100 Score	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	15.4 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 4: 100 - <200 Score	33.3 percentage of subjects	83.3 percentage of subjects	33.3 percentage of subjects	0.0 percentage of subjects	46.2 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 4: 200 - 300 Score	66.7 percentage of subjects	16.7 percentage of subjects	66.7 percentage of subjects	0.0 percentage of subjects	23.1 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 4: Missing	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	100.0 percentage of subjects	15.4 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 5: 0 Score	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 5: >0 - <100 Score	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 5: 100 - <200 Score	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	16.7 percentage of subjects	0.0 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 5: 200 - 300 Score	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	66.7 percentage of subjects	0.0 percentage of subjects
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) Week 5: Missing	100.0 percentage of subjects	100.0 percentage of subjects	100.0 percentage of subjects	16.7 percentage of subjects	100.0 percentage of subjects

SECONDARY outcome

Timeframe: Week 1 (pre-dose) and Week 4.

Population: The Biomarker analysis set consisted of all subjects who received at least 1 administration of Sym004 and who had at least 1 biomarker evaluation.

Outcome measures

Outcome measures
Measure	Part A: Sym004 6 mg/kg n=3 Participants Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 Participants Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 Participants Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=13 Participants Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Percentage of Participants With EGFR Amplification Using Fluorescent in Situ Hybridization (FISH) Method. Week 4: EGFR-FISH Negative	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	23.1 percentage of subjects
Percentage of Participants With EGFR Amplification Using Fluorescent in Situ Hybridization (FISH) Method. Week 4: missing	100.0 percentage of subjects	100.0 percentage of subjects	100.0 percentage of subjects	100.0 percentage of subjects	76.9 percentage of subjects
Percentage of Participants With EGFR Amplification Using Fluorescent in Situ Hybridization (FISH) Method. Week 1: EGFR-FISH Positive	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects
Percentage of Participants With EGFR Amplification Using Fluorescent in Situ Hybridization (FISH) Method. Week 1: EGFR-FISH Negative	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	53.8 percentage of subjects
Percentage of Participants With EGFR Amplification Using Fluorescent in Situ Hybridization (FISH) Method. Week 1: missing	100.0 percentage of subjects	100.0 percentage of subjects	100.0 percentage of subjects	100.0 percentage of subjects	46.2 percentage of subjects
Percentage of Participants With EGFR Amplification Using Fluorescent in Situ Hybridization (FISH) Method. Week 4: EGFR-FISH Positive	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects	0.0 percentage of subjects

Adverse Events

Part A: Sym004 6 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A: Sym004 9/6 mg/kg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part A: Sym004 12 mg/kg

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Part A: Sym004 18 mg/kg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part B: Sym004 12 mg/kg

Serious events: 9 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: Sym004 6 mg/kg n=3 participants at risk Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 participants at risk Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 participants at risk Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 participants at risk Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=30 participants at risk Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Cardiac disorders Cardiac arrest	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Gastrointestinal disorders Dysphagia	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Gastrointestinal disorders Nausea	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Infections and infestations Lung infection	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Injury, poisoning and procedural complications Compression fracture	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations Blood creatinine increased	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea at rest	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary fistula	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Toxic skin eruption	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Vascular disorders Venous thrombosis limb	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks

Other adverse events

Other adverse events
Measure	Part A: Sym004 6 mg/kg n=3 participants at risk Sym004 was administered at a dose of 6 milligram per kilogram (mg/kg) by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 9/6 mg/kg n=6 participants at risk Sym004 was administered at a dose of 9 mg/kg by intravenous infusion at Week 1 followed by a maintenance dose of 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 12 mg/kg n=6 participants at risk Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part A: Sym004 18 mg/kg n=6 participants at risk Sym004 was administered at a dose of 18 mg/kg by intravenous infusion biweekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.	Part B: Sym004 12 mg/kg n=30 participants at risk Sym004 was administered at a dose of 12 mg/kg by intravenous infusion weekly until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Investigations Lymphocyte count decreased	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Blood and lymphatic system disorders Anaemia	66.7% 2/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Blood and lymphatic system disorders Eosinophilia	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Blood and lymphatic system disorders Lymphopenia	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Cardiac disorders Palpitations	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Eye disorders Conjunctival hyperaemia	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Eye disorders Eye discharge	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Gastrointestinal disorders Cheilitis	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Gastrointestinal disorders Constipation	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	23.3% 7/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	50.0% 3/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	13.3% 4/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Gastrointestinal disorders Gingival bleeding	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Gastrointestinal disorders Nausea	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	10.0% 3/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Gastrointestinal disorders Stomatitis	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	50.0% 3/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 10/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Gastrointestinal disorders Vomiting	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
General disorders Face oedema	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	10.0% 3/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
General disorders Fatigue	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	43.3% 13/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
General disorders Malaise	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
General disorders Oedema peripheral	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	13.3% 4/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
General disorders Pyrexia	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Infections and infestations Conjunctivitis	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Infections and infestations Herpes zoster	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Infections and infestations Lung infection	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Infections and infestations Paronychia	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 10/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Infections and infestations Peritonitis	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Injury, poisoning and procedural complications Infusion related reaction	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	30.0% 9/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Injury, poisoning and procedural complications Overdose	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations Alanine aminotransferase increased	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 5/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations Aspartate aminotransferase increased	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 5/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations Blood alkaline phosphatase increased	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	10.0% 3/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations Blood bilirubin increased	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations Blood creatinine increased	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations Blood magnesium decreased	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations Blood urine present	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	10.0% 3/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations Electrocardiogram QT prolonged	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	13.3% 4/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations Platelet count decreased	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations Weight decreased	100.0% 3/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	30.0% 9/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations Weight increased	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	10.0% 3/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Investigations White blood cell count decreased	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Metabolism and nutrition disorders Decreased appetite	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	26.7% 8/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	50.0% 3/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	26.7% 8/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	20.0% 6/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Metabolism and nutrition disorders Hypokalaemia	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Metabolism and nutrition disorders Hypomagnesaemia	100.0% 3/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	100.0% 6/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	83.3% 5/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	83.3% 5/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	66.7% 20/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	10.0% 3/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Nervous system disorders Dysgeusia	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	23.3% 7/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Nervous system disorders Headache	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Nervous system disorders Peripheral motor neuropathy	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Psychiatric disorders Insomnia	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	10.0% 3/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Renal and urinary disorders Haematuria	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	10.0% 3/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Renal and urinary disorders Proteinuria	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	10.0% 3/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Dermatitis acneiform	100.0% 3/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	100.0% 6/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	100.0% 6/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	83.3% 5/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	76.7% 23/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Dry skin	66.7% 2/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	66.7% 4/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	56.7% 17/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Erythema	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Hirsutism	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 5/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	36.7% 11/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Pruritus generalised	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	33.3% 2/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	13.3% 4/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	20.0% 6/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Skin atrophy	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Skin exfoliation	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Skin fissures	33.3% 1/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	3.3% 1/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Vascular disorders Flushing	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Vascular disorders Hypertension	0.00% 0/3 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	16.7% 1/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	0.00% 0/6 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks	6.7% 2/30 • Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks

Additional Information

Merck KGaA Communication Center

Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place