Japanese Phase 1 Trial of Sym004 in Solid Tumors

Sponsor

Merck KGaA, Darmstadt, Germany (Industry)

Overall Status

Completed

CT.gov ID

NCT01955473

Collaborator

(none)

Enrollment

Location

Arm

Actual Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial is to assess the safety and tolerability of Sym004, administered weekly or biweekly as monotherapy in Japanese subjects with advanced solid tumors.This study consisted of two parts, a dose-escalation part ("Part-A") and a dose-expansion part ("Part-B"). In Part-A, Sym004 will be administered weekly or biweekly as monotherapy in Japanese subjects with advanced solid tumors. In Part-B, Sym004 will be administered weekly as monotherapy to Japanese subjects with advanced esophageal squamous cell carcinoma (ESCC) as dose-expansion. A subject will receive Sym004 administration weekly at a dose that will determined to be the MTD or a dose that will lower than the MTD and determined to be appropriate with recommendation by Safety monitoring committee (SMC). The dose going to used in Part-B will be determined after safety confirmation of weekly regimens in Part-A of this trial.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: Sym004	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

51 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Japanese Phase I Open-label Dose-escalation Trial of Sym004 Administered as Monotherapy in Japanese Subjects With Advanced Solid Tumors

Actual Study Start Date :

Oct 31, 2013

Actual Primary Completion Date :

Oct 31, 2015

Actual Study Completion Date :

Oct 31, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sym004	Drug: Sym004 Part-A (dose-escalation): Sym004 will be administered intravenously either weekly at 6 to 12 milligram per kilogram (mg/kg) or biweekly at 18 mg/kg from Week 1 until unacceptable toxicity, disease progression, or consent withdrawal. Part-B (dose-expansion): After the maximum tolerated dose (MTD) is determined in Part-A, up to 30 additional subjects will continue to receive treatment in Part-B.

Arm

Intervention/Treatment

Experimental: Sym004

Drug: Sym004

Part-A (dose-escalation): Sym004 will be administered intravenously either weekly at 6 to 12 milligram per kilogram (mg/kg) or biweekly at 18 mg/kg from Week 1 until unacceptable toxicity, disease progression, or consent withdrawal. Part-B (dose-expansion): After the maximum tolerated dose (MTD) is determined in Part-A, up to 30 additional subjects will continue to receive treatment in Part-B.

Outcome Measures

Primary Outcome Measures

Number of Subjects With Dose Limiting Toxicities (DLTs) Determined in Part-A [Week 1 up to Week 4 (Part A)]
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.
Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death [Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks]
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.

Secondary Outcome Measures

Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) at Week 1: Single Dose [Pre-infusion, end of infusion, 4, 8, 12, 24, 48 and 168 hours post-infusion at Week 1]
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 AUC are presented for both monoclonal antibodies.
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 [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 AUC are presented for both monoclonal antibodies. 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.
Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) at Week 1: Single Dose [Pre-infusion, end of infusion, 4, 8, 12, 24, 48 and 168 hours post-infusion at Week 1]
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.
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 [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.
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 [Pre-infusion, end of infusion, 4, 8, 12, 24, 48, 168, 336 hours post-infusion at Week 1]
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 AUC are presented for both monoclonal antibodies. Results were to be assessed for biweekly dosing cohort (Part A: Sym004 18 mg/kg) only.
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 [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 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 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 [Pre-infusion, end of infusion, 4, 8, 12, 24, 48, 168, 336 hours post-infusion at Week 1]
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.
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 [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.
Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 1: Single Dose [Pre-infusion, end of infusion, 4, 8, 12, 24, and 48 hours post-infusion at Week 1]
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 AUC are presented for both monoclonal antibodies. Results were to be assessed for biweekly dosing cohort (Part A: Sym004 18 mg/kg) only.
Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 5: Multiple Dose [Pre-infusion, end of infusion, 4, 8, 12 and 24 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 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 Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) at Week 1: Single Dose [Pre-infusion, end of infusion, 4, 8, 12, 24, and 48 hours post-infusion at Week 1]
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-inf was calculated as AUC(0-inf)/Dose.
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 [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.
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 [Pre-infusion, end of infusion, 4, 8, 12, 24 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. 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.
Terminal Half-life (t1/2) of Sym004 at Week 1: Single Dose [Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1]
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.
Terminal Half-life (t1/2) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose [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.
Terminal Half-life (t1/2) of Sym004 For the Biweekly Regimen at Week 5: Multiple Dose [Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5]
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.
Clearance (CL) of Sym004 at Week 1: Single Dose [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.
Clearance at Steady-state (CLss) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose [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.
Clearance at Steady-state (CLss) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose [Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5]
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.
Volume of Distribution at the Elimination Phase (Vz) of Sym004 at Week 1: Single Dose [Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1]
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). Vz are presented for both monoclonal antibodies.
Volume of Distribution at Steady State (Vss) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose [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.
Volume of Distribution at Steady State (Vss) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose [Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5]
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.
Maximum Serum Concentration (Cmax) of Sym004 at Week 1: Single Dose [Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1]
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.
Maximum Serum Concentration (Cmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose [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). 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.
Maximum Serum Concentration (Cmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose [Pre-infusion, end of infusion, 4, 8, 12, 24 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). 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 Maximum Serum Concentration (Cmax) of Sym004 at Week 1: Single Dose [Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1]
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). Dose Normalized Cmax are presented for both monoclonal antibodies. Dose normalized Cmax was calculated as Cmax/Dose.
Dose Nornamized Maximum Serum Concentration (Cmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose [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 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.
Dose Normalized Maximum Serum Concentration (Cmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose [Pre-infusion, end of infusion, 4, 8, 12, 24 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 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.
Trough Concentrations (Ctrough) of Sym004 [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)]
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). Ctrough are presented for both monoclonal antibodies.
Time to Reach Maximum Concentration (Tmax) of Sym004 at Week 1: Single Dose [Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1]
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.
Time to Reach Maximum Concentration (Tmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose [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). 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.
Time to Reach Maximum Concentration (Tmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose [Pre-infusion, end of infusion, 4, 8, 12, 24 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). 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.
Percentage of Subjects With Best Overall Response [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 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.
Duration of Overall Response [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.
Percentage of Subjects With Disease Control [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.
Duration of Disease Control [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.
Time to Progression [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.
Progression-free Survival Time [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.
Anti-drug Antibody Titers [Week 1 (pre-dose) up to Follow-up assessment (up to maximum 45.1 Weeks)]
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) [Week 1 (pre-dose), Week 4 and Week 5]
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.
Percentage of Participants With EGFR Amplification Using Fluorescent in Situ Hybridization (FISH) Method. [Week 1 (pre-dose) and Week 4.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Japanese male or female subjects aged greater than or equal to 20 years at the time of informed consent signature
Histologically or cytologically confirmed cancer
Refractory or recurrent advanced late stage solid tumors without available therapeutic options which are likely to provide patient benefit (failure and/or intolerance to standard anti-cancer therapy)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Life expectancy of at least 3 months
Written informed consent given before any trial-related activities are carried out
Other protocol defined inclusion criteria could apply

Exclusion Criteria:

Subjects with symptomatic brain metastases
Subjects who received total resection or irradiation of the target lesion
Received any of the following medications within 4 weeks before the first administration of Sym004 at Week 1: cytotoxic or cytostatic anti-cancer therapy, antibody therapy, tyrosine kinase inhibitors, and any investigational agent
Received vaccine therapy as anticancer treatment within 12 weeks before the first administration of Sym004 at Week 1
Diarrhea of greater than Grade 1 according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 (v4.03)
Skin manifestation of greater than Grade 1 according to NCI-CTCAE (v4.03)
Magnesium of less than 0.9 milligram per deciliter (mg/dL)
Abnormal organ or bone marrow function as defined in the protocol
Received immunosuppressive agents (including systemic corticosteroids used at doses above 20 milligram per day (mg/day) of prednisolone or equivalent) within 4 weeks before the first administration of Sym004 at Week 1
Active severe infection, any other concurrent disease or medical conditions that are deemed to interfere with the conduct of the trial as judged by the Investigator
Known human immunodeficiency virus (HIV) positive, active Hepatitis B or C, or uncontrolled allergic conditions or allergy to Sym004 or its components
Clinically significant cardiac disease or concurrent, uncontrolled medical condition
Known previous Grade 3 to 4 infusion-related reactions, according to NCI-CTCAE (v4.03), with chimeric monoclonal antibodies
Other protocol defined exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Please contact the Merck KGaA Communication Center located in	Darmstadt		Germany

Sponsors and Collaborators

Merck KGaA, Darmstadt, Germany

Investigators

Study Director: Medical Responsible, Merck Serono Co., Ltd. Japan, an business of Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Merck KGaA, Darmstadt, Germany

ClinicalTrials.gov Identifier:

NCT01955473

Other Study ID Numbers:

EMR 200637-001

First Posted:

Oct 7, 2013

Last Update Posted:

Aug 23, 2017

Last Verified:

Jul 1, 2017

Keywords provided by Merck KGaA, Darmstadt, Germany

Solid tumors

Sym004

Phase 1

Additional relevant MeSH terms:

Neoplasms

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	A total of 60 subjects were screened for eligibility, out of which and 51 subjects were randomized into the study.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Period Title: Overall Study
STARTED	3	6	6	6	30
COMPLETED	3	6	6	6	30
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg	Total
Arm/Group Description	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.	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.	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.	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.	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 of all reporting groups
Overall Participants	3	6	6	6	30	51
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.7 (3.51)	62.5 (5.09)	66.5 (5.96)	59.0 (9.32)	61.2 (7.20)	61.6 (7.03)
Sex: Female, Male (Count of Participants)
Female	2 66.7%	1 16.7%	3 50%	0 0%	6 20%	12 23.5%
Male	1 33.3%	5 83.3%	3 50%	6 100%	24 80%	39 76.5%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Dose Limiting Toxicities (DLTs) Determined in Part-A
Description	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.
Time Frame	Week 1 up to Week 4 (Part A)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	3	6	6	6
Number [subjects]	0	0	0	0

2. Primary Outcome

Title	Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death
Description	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.
Time Frame	Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks

Outcome Measure Data

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

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	30
TEAEs	3	6	6	6	30
Serious TEAEs	0	0	2	0	9
TEAE leading to Discontinuation	0	0	0	0	4
TEAEs Leading to Death	0	0	0	0	3

3. Secondary Outcome

Title	Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) at Week 1: Single Dose
Description	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 AUC are presented for both monoclonal antibodies.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, 48 and 168 hours post-infusion at Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	7
mAb992	3685.5 (38.1)	5893.1 (33.3)	8957.3 (29.3)	12783 (26.0)	7073.5 (15.1)
mAb1024	4109.0 (25.6)	6572.1 (30.5)	10213 (24.1)	15917 (30.6)	10336 (27.4)

4. Secondary Outcome

Title	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
Description	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 AUC are presented for both monoclonal antibodies. 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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, and 168 hours post-infusion at Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.
Measure Participants	2	5	6	5
mAb992 (n=2, 5, 6, 5)	NA (NA)	7111.1 (41.7)	15298 (41.4)	13053 (18.7)
mAb1024 (n=2, 4, 6, 5)	NA (NA)	9738.5 (36.8)	21422 (45.5)	22016 (32.2)

5. Secondary Outcome

Title	Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) at Week 1: Single Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, 48 and 168 hours post-infusion at Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	7
mAb992	22.50 (29.5)	23.24 (30.7)	25.79 (18.0)	21.69 (24.8)	22.70 (17.5)
mAb1024	25.09 (20.1)	25.91 (27.7)	29.41 (11.1)	27.01 (26.0)	33.17 (27.8)

6. Secondary Outcome

Title	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
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, and 168 hours post-infusion at Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.
Measure Participants	2	5	6	5
mAb992 (n= 2, 5, 6, 5)	NA (NA)	43.90 (27.3)	43.45 (29.3)	42.38 (15.0)
mAb1024 (n= 2, 4, 6, 5)	NA (NA)	59.12 (30.6)	60.85 (32.9)	72.36 (28.2)

7. Secondary Outcome

Title	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
Description	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 AUC are presented for both monoclonal antibodies. Results were to be assessed for biweekly dosing cohort (Part A: Sym004 18 mg/kg) only.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, 48, 168, 336 hours post-infusion at Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	6
mAb992	17318 (27.0)
mAb1024	22458 (29.7)

8. Secondary Outcome

Title	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
Description	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 AUC are presented for both monoclonal antibodies. Results were to be assessed for biweekly dosing cohort (Part A: Sym004 18 mg/kg) only.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, 168 and 336 hours post-infusion at Week 5

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	5
mAb992	24755 (31.8)
mAb1024	32336 (30.8)

9. Secondary Outcome

Title	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
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, 48, 168, 336 hours post-infusion at Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	6
mAb992	29.39 (27.1)
mAb1024	38.11 (26.9)

10. Secondary Outcome

Title	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
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, 168 and 336 hours post-infusion at Week 5

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	5
mAb992	42.45 (29.9)
mAb1024	55.46 (25.7)

11. Secondary Outcome

Title	Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 1: Single Dose
Description	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 AUC are presented for both monoclonal antibodies. Results were to be assessed for biweekly dosing cohort (Part A: Sym004 18 mg/kg) only.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, and 48 hours post-infusion at Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	6
mAb992	19896 (28.9)
mAb1024	27554 (30.7)

12. Secondary Outcome

Title	Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 5: Multiple Dose
Description	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 AUC are presented for both monoclonal antibodies. Results were to be assessed for biweekly dosing cohort (Part A: Sym004 18 mg/kg) only.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12 and 24 hours post-infusion at Week 5

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	5
mAb992	30127 (36.6)
mAb1024	43308 (37.8)

13. Secondary Outcome

Title	Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) at Week 1: Single Dose
Description	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-inf was calculated as AUC(0-inf)/Dose.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, and 48 hours post-infusion at Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	7
mAb992 (3, 6, 6, 6, 7)	27.30 (26.7)	30.33 (37.7)	34.471 (22.5)	33.77 (30.3)	31.05 (24.6)
mAb1024 (3, 6, 6, 6, 6)	31.86 (21.9)	36.20 (37.4)	43.41 (23.1)	46.77 (30.9)	47.48 (17.5)

14. Secondary Outcome

Title	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
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.
Measure Participants	2	5	6	5
mAb992 (n= 1, 5, 6, 5)	NA (NA)	59.65 (37.3)	77.86 (65.2)	72.22 (17.1)
mAb1024 (n= 2, 4, 6, 4)	NA (NA)	94.91 (44.7)	118.1 (57.5)	136.9 (46.8)

15. Secondary Outcome

Title	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
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	5
mAb992	51.67 (36.2)
mAb1024	74.28 (36.3)

16. Secondary Outcome

Title	Terminal Half-life (t1/2) of Sym004 at Week 1: Single Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	7
mAb992 (n= 3,6,6,6,7)	66.478 (10.0)	79.041 (18.8)	82.865 (21.1)	111.69 (18.9)	87.257 (21.1)
mAb1024 (n= 3,6,6,6,6)	74.075 (8.8)	91.303 (21.7)	100.05 (24.3)	134.48 (27.8)	100.57 (34.8)

17. Secondary Outcome

Title	Terminal Half-life (t1/2) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.
Measure Participants	2	5	6	5
mAb992 (n= 1, 5, 6, 5)	NA (NA)	85.228 (24.4)	135.98 (52.5)	132.14 (13.9)
mAb1024 (n= 2, 4, 6, 4)	NA (NA)	117.8 (27.5)	155.9 (37.4)	163.8 (27.5)

18. Secondary Outcome

Title	Terminal Half-life (t1/2) of Sym004 For the Biweekly Regimen at Week 5: Multiple Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	5
mAb992	130.39 (26.4)
mAb1024	163.6 (36.3)

19. Secondary Outcome

Title	Clearance (CL) of Sym004 at Week 1: Single Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	7
mAb992 (n= 3,6,6,6,7)	0.036626 (26.7)	0.032967 (37.7)	0.029012 (22.5)	0.029615 (30.3)	0.032202 (24.6)
mAb1024 (n= 3,6,6,6,6)	0.031385 (21.9)	0.027622 (37.4)	0.023033 (23.1)	0.021383 (30.9)	0.021058 (17.6)

20. Secondary Outcome

Title	Clearance at Steady-state (CLss) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.
Measure Participants	2	5	6	5
mAb992 (n= 2, 5, 6, 5)	NA (NA)	0.022778 (27.3)	0.023015 (29.3)	0.023589 (15.0)
mAb1024 (n= 2, 4, 6, 4)	NA (NA)	0.017 (30.6)	0.016 (32.9)	0.014 (28.2)

21. Secondary Outcome

Title	Clearance at Steady-state (CLss) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	5
mAb992	0.023552 (29.9)
mAb1024	0.018 (25.6)

22. Secondary Outcome

Title	Volume of Distribution at the Elimination Phase (Vz) of Sym004 at Week 1: Single Dose
Description	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). Vz are presented for both monoclonal antibodies.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	7
mAb992 (n= 3,6,6,6,7)	3.5130 (36.1)	3.7593 (21.9)	3.4688 (17.8)	4.7726 (23.3)	4.0536 (10.8)
mAb1024 (n= 3,6,6,6,6)	3.3543 (16.7)	3.6384 (17.6)	3.3245 (3.4)	4.1483 (29.1)	3.0558 (47.0)

23. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.
Measure Participants	2	5	6	5
mAb992 (n= 1, 5, 6, 5)	NA (NA)	2.7931 (15.4)	4.4777 (26.2)	4.4383 (17.9)
mAb1024 (n= 2, 4, 6, 4)	NA (NA)	2.85 (20.6)	3.71 (21.3)	3.40 (24.9)

24. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	5
mAb992	4.3988 (24.4)
mAb1024	4.20 (27.7)

25. Secondary Outcome

Title	Maximum Serum Concentration (Cmax) of Sym004 at Week 1: Single Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	7
mAb992	50.131 (29.2)	85.088 (25.3)	120.37 (33.6)	157.71 (18.6)	88.589 (15.0)
mAb1024	54.660 (15.6)	89.443 (26.2)	116.18 (31.2)	187.03 (23.9)	146.92 (56.3)

26. Secondary Outcome

Title	Maximum Serum Concentration (Cmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.
Measure Participants	3	6	6	6
mAb992	76.094 (16.4)	86.763 (34.0)	181.62 (31.6)	143.79 (23.4)
mAb1024	89.26 (10.2)	91.70 (33.4)	221.3 (21.1)	231.9 (32.8)

27. Secondary Outcome

Title	Maximum Serum Concentration (Cmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	6
mAb992	187.40 (24.3)
mAb1024	224.0 (24.7)

28. Secondary Outcome

Title	Dose Normalized Maximum Serum Concentration (Cmax) of Sym004 at Week 1: Single Dose
Description	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). Dose Normalized Cmax are presented for both monoclonal antibodies. Dose normalized Cmax was calculated as Cmax/Dose.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	7
mAb992	0.306 (19.8)	0.336 (23.5)	0.346 (22.0)	0.268 (19.1)	0.284 (13.0)
mAb1024	0.334 (8.4)	0.353 (26.0)	0.334 (13.4)	0.317 (15.6)	0.471 (58.7)

29. Secondary Outcome

Title	Dose Nornamized Maximum Serum Concentration (Cmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.
Measure Participants	3	6	6	6
mAb992	0.486 (4.4)	0.524 (31.4)	0.516 (18.4)	0.466 (12.8)
mAb1024	0.570 (7.1)	0.553 (32.3)	0.629 (12.9)	0.752 (24.3)

30. Secondary Outcome

Title	Dose Normalized Maximum Serum Concentration (Cmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	6
mAb992	0.318 (25.0)
mAb1024	0.380 (20.2)

31. Secondary Outcome

Title	Trough Concentrations (Ctrough) of Sym004
Description	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). Ctrough are presented for both monoclonal antibodies.
Time Frame	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 Measure Data

Analysis Population Description
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 time frame.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	29
mAb992 Week 2 pre-dose (n= 3, 6, 6, 6, 29)	8.38333 (2.562935)	16.3617 (7.384964)	29.4483 (9.716758)	45.1117 (17.24716)	20.1517 (8.411459)
mAb992 Week 3 pre-dose (n= 3, 6, 5, 6, 26)	19.8700 (9.570564)	16.7033 (8.283479)	57.7280 (29.34743)	15.3600 (6.817337)	32.6969 (12.62782)
mAb992 Week 5 pre-dose (n= 2, 5, 6, 0, 23)	NA (NA)	22.9260 (11.37231)	66.0267 (37.84088)	NA (NA)	71.0739 (67.33365)
mAb992 Week 6 pre-dose (n= 3, 5, 5, 4, 21)	25.5833 (21.14422)	26.3340 (13.43829)	92.4920 (47.20264)	64.3750 (20.56197)	53.2224 (30.76489)
mAb992 Week 7 pre-dose (n= 2, 4, 4, 4, 21)	NA (NA)	25.7500 (16.36742)	70.9875 (61.05280)	36.1700 (7.608184)	66.1524 (65.22446)
mAb992 Week 8 pre-dose (n= 2, 4, 3, 2, 12)	NA (NA)	24.8650 (13.70631)	122.283 (79.73053)	NA (NA)	60.4542 (25.37663)
mAb992 End of Trial(up to 41.1weeks)(n=3,6,6,6,27)	NA (NA)	NA (NA)	13.8400 (32.25929)	1.24833 (2.197339)	5.63333 (11.64986)
mAb992 Follow up (up to 45.1 Weeks)(n=1,2,3,4,19)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
mAb1024 Week 2 pre-dose (n= 3, 6, 6, 6, 29)	10.6767 (2.688128)	20.2433 (8.704451)	38.7017 (12.01645)	58.6967 (17.29509)	27.8641 (12.33288)
mAb1024 Week 3 pre-dose (n= 3, 6, 5, 6, 26)	23.8000 (9.525382)	22.7517 (14.69928)	69.9460 (21.36079)	24.7000 (11.16315)	44.6531 (17.91820)
mAb1024 Week 5 pre-dose (n= 2, 5, 6, 0, 23)	NA (NA)	31.8900 (17.43852)	98.6550 (46.85021)	NA (NA)	82.6235 (49.01981)
mAb1024 Week 6 pre-dose (n= 3, 5, 5, 4, 21)	31.8700 (23.97075)	35.2440 (18.90163)	128.858 (41.31495)	90.9275 (26.82442)	80.0024 (35.72029)
mAb1024 Week 7 pre-dose (n= 2, 4, 4, 4, 21)	NA (NA)	36.1125 (24.42487)	107.843 (76.48666)	54.9275 (13.15679)	94.4729 (52.58200)
mAb1024 Week 8 pre-dose (n= 2, 4, 3, 2, 12)	NA (NA)	34.6050 (19.49550)	166.207 (52.87010)	NA (NA)	93.0283 (47.35483)
mAb1024End of Trial(up to 41.1weeks)(n=3,6,6,6,27)	NA (NA)	NA (NA)	25.4667 (58.32014)	3.73333 (6.795639)	11.2478 (19.88056)
mAb1024 Follow up (up to 45.1 Weeks)(n=1,2,3,4,19)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)

32. Secondary Outcome

Title	Time to Reach Maximum Concentration (Tmax) of Sym004 at Week 1: Single Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24, 48 hours post-infusion at Week 1

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	7
mAb992	2.07	5.12	5.73	7.21	6.30
mAb1024	2.05	7.20	6.66	7.15	7.13

33. Secondary Outcome

Title	Time to Reach Maximum Concentration (Tmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 4

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.
Measure Participants	3	6	6	6
mAb992	10.1	5.94	9.13	5.13
mAb1024	2.07	6.13	5.18	7.10

34. Secondary Outcome

Title	Time to Reach Maximum Concentration (Tmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose
Description	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.
Time Frame	Pre-infusion, end of infusion, 4, 8, 12, 24 hours post-infusion at Week 5

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 18 mg/kg
Arm/Group Description	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.
Measure Participants	6
mAb992	7.03
mAb1024	5.28

35. Secondary Outcome

Title	Percentage of Subjects With Best Overall Response
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	30
CR	0	0	0	0	0
PR	0	0	33.3	0	16.7

36. Secondary Outcome

Title	Duration of Overall Response
Description	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.
Time Frame	Week 7 and thereafter every 6 weeks until the first date of objectively documented recurrent or progressive disease, up to 45.1 Weeks

Outcome Measure Data

Analysis Population Description
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. Here, "Number of Participants Analyzed" signifies those subjects who achieved confirmed CR or PR.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	0	0	2	0	5
Median (Full Range) [Weeks]	25.85	10.40

37. Secondary Outcome

Title	Percentage of Subjects With Disease Control
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	30
Number (95% Confidence Interval) [percentage of subjects]	66.7	66.7	50.0	16.7	56.7

38. Secondary Outcome

Title	Duration of Disease Control
Description	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.
Time Frame	Week 7 and thereafter every 6 weeks until the first date of objectively documented recurrent or progressive disease, up to 45.1 weeks

Outcome Measure Data

Analysis Population Description
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. Here, "Number of Participants Analyzed" signifies those subjects who achieved disease control.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	2	4	3	1	17
Median (Full Range) [Weeks]	6.10	5.35	24.60	6.10	5.90

39. Secondary Outcome

Title	Time to Progression
Description	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.
Time Frame	Time from enrollment until the date of objectively documented disease progression or death, up to 45.1 Weeks

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part B: Sym004 12 mg/kg	Part A and B Combined
Arm/Group Description	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.	All subjects who were included in Part A and Part B. Sym004 administered by intravenous infusion at a dose of 6 mg/kg weekly, or 9 mg/kg at Week 1 followed by a maintenance dose of 6 mg/kg weekly, or 12 mg/kg weekly, or 18 mg/kg biweekly in Part A or 12 mg/kg by intravenous infusion weekly in Part B until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Measure Participants	30	51
Median (95% Confidence Interval) [months]	2.37	2.33

40. Secondary Outcome

Title	Progression-free Survival Time
Description	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.
Time Frame	Time from enrollment until the date of objectively documented disease progression or death, up to 45.1 Weeks

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part B: Sym004 12 mg/kg	Part A and B Combined
Arm/Group Description	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.	All subjects who were included in Part A and Part B. Sym004 administered by intravenous infusion at a dose of 6 mg/kg weekly, or 9 mg/kg at Week 1 followed by a maintenance dose of 6 mg/kg weekly, or 12 mg/kg weekly, or 18 mg/kg biweekly in Part A or 12 mg/kg by intravenous infusion weekly in Part B until unacceptable toxicity, disease progression, or consent withdrawal, or until the subject met any of the criteria for treatment or trial discontinuation.
Measure Participants	30	51
Median (95% Confidence Interval) [months]	2.12	2.30

41. Secondary Outcome

Title	Anti-drug Antibody Titers
Description
Time Frame	Week 1 (pre-dose) up to Follow-up assessment (up to maximum 45.1 Weeks)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	0	0	0	0	0

42. Secondary Outcome

Title	Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC)
Description	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.
Time Frame	Week 1 (pre-dose), Week 4 and Week 5

Outcome Measure Data

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

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	13
Week 1: 0 Score	0.0	0.0	0.0	0.0	7.7
Week 1: greater than (>) 0-less than(<) 100 Score	0.0	0.0	0.0	0.0	0.0
Week 1: 100 - <200 Score	33.3	0.0	16.7	0.0	0.0
Week 1: 200 - 300 Score	66.7	83.3	83.3	100.0	76.9
Week 1: Missing	0.0	16.7	0.0	0.0	15.4
Week 4: 0 Score	0.0	0.0	0.0	0.0	0.0
Week 4: >0 - <100 Score	0.0	0.0	0.0	0.0	15.4
Week 4: 100 - <200 Score	33.3	83.3	33.3	0.0	46.2
Week 4: 200 - 300 Score	66.7	16.7	66.7	0.0	23.1
Week 4: Missing	0.0	0.0	0.0	100.0	15.4
Week 5: 0 Score	0.0	0.0	0.0	0.0	0.0
Week 5: >0 - <100 Score	0.0	0.0	0.0	0.0	0.0
Week 5: 100 - <200 Score	0.0	0.0	0.0	16.7	0.0
Week 5: 200 - 300 Score	0.0	0.0	0.0	66.7	0.0
Week 5: Missing	100.0	100.0	100.0	16.7	100.0

43. Secondary Outcome

Title	Percentage of Participants With EGFR Amplification Using Fluorescent in Situ Hybridization (FISH) Method.
Description
Time Frame	Week 1 (pre-dose) and Week 4.

Outcome Measure Data

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

Arm/Group Title	Part A: Sym004 6 mg/kg	Part A: Sym004 9/6 mg/kg	Part A: Sym004 12 mg/kg	Part A: Sym004 18 mg/kg	Part B: Sym004 12 mg/kg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	6	6	6	13
Week 1: EGFR-FISH Positive	0.0	0.0	0.0	0.0	0.0
Week 1: EGFR-FISH Negative	0.0	0.0	0.0	0.0	53.8
Week 1: missing	100.0	100.0	100.0	100.0	46.2
Week 4: EGFR-FISH Positive	0.0	0.0	0.0	0.0	0.0
Week 4: EGFR-FISH Negative	0.0	0.0	0.0	0.0	23.1
Week 4: missing	100.0	100.0	100.0	100.0	76.9

Adverse Events

	Part A: Sym004 6 mg/kg		Part A: Sym004 9/6 mg/kg		Part A: Sym004 12 mg/kg		Part A: Sym004 18 mg/kg		Part B: Sym004 12 mg/kg
Time Frame	Baseline up to 4 weeks after the last Sym004 administration, up to a maximum of 41.1 weeks
Adverse Event Reporting Description

Arm/Group Title	Part A: Sym004 6 mg/kg		Part A: Sym004 9/6 mg/kg		Part A: Sym004 12 mg/kg		Part A: Sym004 18 mg/kg		Part B: Sym004 12 mg/kg
Arm/Group Description	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.		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.		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.		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.		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.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part A: Sym004 6 mg/kg		Part A: Sym004 9/6 mg/kg		Part A: Sym004 12 mg/kg		Part A: Sym004 18 mg/kg		Part B: Sym004 12 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/6 (0%)		2/6 (33.3%)		0/6 (0%)		9/30 (30%)
Cardiac disorders
Cardiac arrest	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/30 (3.3%)
Gastrointestinal disorders
Dysphagia	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/30 (3.3%)
Nausea	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/30 (3.3%)
Infections and infestations
Lung infection	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/30 (3.3%)
Injury, poisoning and procedural complications
Compression fracture	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/30 (0%)
Investigations
Blood creatinine increased	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/30 (3.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/30 (3.3%)
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/30 (3.3%)
Dyspnoea at rest	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/30 (3.3%)
Interstitial lung disease	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/30 (3.3%)
Pulmonary fistula	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/30 (3.3%)
Skin and subcutaneous tissue disorders
Toxic skin eruption	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/30 (3.3%)
Vascular disorders
Venous thrombosis limb	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Part A: Sym004 6 mg/kg		Part A: Sym004 9/6 mg/kg		Part A: Sym004 12 mg/kg		Part A: Sym004 18 mg/kg		Part B: Sym004 12 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		6/6 (100%)		6/6 (100%)		6/6 (100%)		30/30 (100%)
Blood and lymphatic system disorders
Anaemia	2/3 (66.7%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/30 (3.3%)
Eosinophilia	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/30 (3.3%)
Lymphopenia	1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/30 (6.7%)
Cardiac disorders
Palpitations	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/30 (0%)
Eye disorders
Conjunctival hyperaemia	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/30 (0%)
Eye discharge	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/30 (6.7%)
Gastrointestinal disorders
Cheilitis	1/3 (33.3%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/30 (3.3%)
Constipation	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		7/30 (23.3%)
Diarrhoea	0/3 (0%)		1/6 (16.7%)		3/6 (50%)		1/6 (16.7%)		4/30 (13.3%)
Gingival bleeding	0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/30 (0%)
Nausea	1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		3/30 (10%)
Stomatitis	1/3 (33.3%)		3/6 (50%)		2/6 (33.3%)		0/6 (0%)		10/30 (33.3%)
Vomiting	1/3 (33.3%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/30 (3.3%)
General disorders
Face oedema	0/3 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		3/30 (10%)
Fatigue	1/3 (33.3%)		0/6 (0%)		2/6 (33.3%)		1/6 (16.7%)		13/30 (43.3%)
Malaise	1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/30 (3.3%)
Oedema peripheral	0/3 (0%)		1/6 (16.7%)		2/6 (33.3%)		1/6 (16.7%)		4/30 (13.3%)
Pyrexia	0/3 (0%)		0/6 (0%)		2/6 (33.3%)		1/6 (16.7%)		2/30 (6.7%)
Infections and infestations
Conjunctivitis	0/3 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		0/30 (0%)
Herpes zoster	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/30 (0%)
Lung infection	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/30 (6.7%)
Paronychia	1/3 (33.3%)		1/6 (16.7%)		2/6 (33.3%)		2/6 (33.3%)		10/30 (33.3%)
Peritonitis	0/3 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/30 (0%)
Injury, poisoning and procedural complications
Infusion related reaction	1/3 (33.3%)		2/6 (33.3%)		2/6 (33.3%)		2/6 (33.3%)		9/30 (30%)
Overdose	0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/30 (0%)
Investigations
Alanine aminotransferase increased	0/3 (0%)		1/6 (16.7%)		2/6 (33.3%)		1/6 (16.7%)		5/30 (16.7%)
Aspartate aminotransferase increased	0/3 (0%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		5/30 (16.7%)
Blood alkaline phosphatase increased	1/3 (33.3%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		3/30 (10%)
Blood bilirubin increased	1/3 (33.3%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/30 (0%)
Blood creatinine increased	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/30 (3.3%)
Blood magnesium decreased	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/30 (6.7%)
Blood urine present	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		3/30 (10%)
Electrocardiogram QT prolonged	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		4/30 (13.3%)
Lymphocyte count decreased	0/3 (0%)		0/6 (0%)		2/6 (33.3%)		0/6 (0%)		1/30 (3.3%)
Platelet count decreased	0/3 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/30 (0%)
Weight decreased	3/3 (100%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		9/30 (30%)
Weight increased	0/3 (0%)		0/6 (0%)		2/6 (33.3%)		1/6 (16.7%)		3/30 (10%)
White blood cell count decreased	1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/30 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/3 (33.3%)		0/6 (0%)		2/6 (33.3%)		0/6 (0%)		8/30 (26.7%)
Dehydration	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/30 (3.3%)
Hyperkalaemia	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/30 (3.3%)
Hypernatraemia	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		2/30 (6.7%)
Hypoalbuminaemia	0/3 (0%)		1/6 (16.7%)		3/6 (50%)		2/6 (33.3%)		8/30 (26.7%)
Hypocalcaemia	0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		6/30 (20%)
Hypokalaemia	1/3 (33.3%)		0/6 (0%)		2/6 (33.3%)		0/6 (0%)		2/30 (6.7%)
Hypomagnesaemia	3/3 (100%)		6/6 (100%)		5/6 (83.3%)		5/6 (83.3%)		20/30 (66.7%)
Hyponatraemia	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		3/30 (10%)
Musculoskeletal and connective tissue disorders
Back pain	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		2/30 (6.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/3 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/30 (0%)
Nervous system disorders
Dysgeusia	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		7/30 (23.3%)
Headache	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/30 (6.7%)
Peripheral motor neuropathy	0/3 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/30 (0%)
Peripheral sensory neuropathy	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/30 (3.3%)
Psychiatric disorders
Insomnia	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		3/30 (10%)
Renal and urinary disorders
Haematuria	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		3/30 (10%)
Proteinuria	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		2/30 (6.7%)
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/30 (6.7%)
Dyspnoea	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		2/30 (6.7%)
Epistaxis	0/3 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		3/30 (10%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	3/3 (100%)		6/6 (100%)		6/6 (100%)		5/6 (83.3%)		23/30 (76.7%)
Dry skin	2/3 (66.7%)		2/6 (33.3%)		0/6 (0%)		4/6 (66.7%)		17/30 (56.7%)
Erythema	0/3 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/30 (0%)
Hirsutism	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/30 (0%)
Pain of skin	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/30 (6.7%)
Palmar-plantar erythrodysaesthesia syndrome	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		5/30 (16.7%)
Pruritus	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		11/30 (36.7%)
Pruritus generalised	1/3 (33.3%)		2/6 (33.3%)		0/6 (0%)		0/6 (0%)		0/30 (0%)
Rash	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		4/30 (13.3%)
Rash maculo-papular	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		6/30 (20%)
Skin atrophy	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/30 (0%)
Skin exfoliation	0/3 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/30 (3.3%)
Skin fissures	1/3 (33.3%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		1/30 (3.3%)
Skin hyperpigmentation	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/30 (0%)
Vascular disorders
Flushing	0/3 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/30 (0%)
Hypertension	0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		2/30 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title	Merck KGaA Communication Center
Organization	Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Phone	+49-6151-72-5200
Email	service@merckgroup.com

Responsible Party:

Merck KGaA, Darmstadt, Germany

ClinicalTrials.gov Identifier:

NCT01955473

Other Study ID Numbers:

EMR 200637-001

First Posted:

Oct 7, 2013

Last Update Posted:

Aug 23, 2017

Last Verified:

Jul 1, 2017

Japanese Phase 1 Trial of Sym004 in Solid Tumors

Study Details

Study Description

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Arms and Interventions

Outcome Measures

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Inclusion Criteria:

Exclusion Criteria:

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Adverse Events

All Cause Mortality

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Results Point of Contact