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OpenTrials
Completed

NCT Number: NCT01955473

Japanese Phase 1 Trial of Sym004 in Solid Tumors

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.

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Key information

Conditions

Solid Tumors

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Please contact the Merck KGaA Communication Center located in

Darmstadt, Germany

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sym004

Drug

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.

Primary outcomes

  1. Number of Subjects With Dose Limiting Toxicities (DLTs) Determined in Part-A

    Time frame: 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.

  2. Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death

    Time frame: 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 outcomes

  1. Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) at Week 1: Single Dose

    Time frame: 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.

  2. 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

    Time frame: 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.

  3. Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) at Week 1: Single Dose

    Time frame: 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.

  4. 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

    Time frame: 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.

  5. 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

    Time frame: 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.

  6. 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

    Time frame: 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.

  7. 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

    Time frame: 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.

  8. 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

    Time frame: 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.

  9. Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 1: Single Dose

    Time frame: 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.

  10. Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 5: Multiple Dose

    Time frame: 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.

  11. Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) at Week 1: Single Dose

    Time frame: 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.

  12. 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

    Time frame: 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.

  13. 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

    Time frame: 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.

  14. Terminal Half-life (t1/2) of Sym004 at Week 1: Single Dose

    Time frame: 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.

  15. Terminal Half-life (t1/2) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose

    Time frame: 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.

  16. Terminal Half-life (t1/2) of Sym004 For the Biweekly Regimen at Week 5: Multiple Dose

    Time frame: 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.

  17. Clearance (CL) of Sym004 at Week 1: Single Dose

    Time frame: 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.

  18. Clearance at Steady-state (CLss) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose

    Time frame: 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.

  19. Clearance at Steady-state (CLss) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose

    Time frame: 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.

  20. Volume of Distribution at the Elimination Phase (Vz) of Sym004 at Week 1: Single Dose

    Time frame: 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.

  21. Volume of Distribution at Steady State (Vss) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose

    Time frame: 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.

  22. Volume of Distribution at Steady State (Vss) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose

    Time frame: 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.

  23. Maximum Serum Concentration (Cmax) of Sym004 at Week 1: Single Dose

    Time frame: 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.

  24. Maximum Serum Concentration (Cmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose

    Time frame: 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.

  25. Maximum Serum Concentration (Cmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose

    Time frame: 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.

  26. Dose Normalized Maximum Serum Concentration (Cmax) of Sym004 at Week 1: Single Dose

    Time frame: 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.

  27. Dose Nornamized Maximum Serum Concentration (Cmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose

    Time frame: 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.

  28. Dose Normalized Maximum Serum Concentration (Cmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose

    Time frame: 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.

  29. Trough Concentrations (Ctrough) of Sym004

    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)

    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.

  30. Time to Reach Maximum Concentration (Tmax) of Sym004 at Week 1: Single Dose

    Time frame: 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.

  31. Time to Reach Maximum Concentration (Tmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose

    Time frame: 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.

  32. Time to Reach Maximum Concentration (Tmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose

    Time frame: 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.

  33. Percentage of Subjects With Best Overall Response

    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)

    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.

  34. Duration of Overall Response

    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

    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.

  35. Percentage of Subjects With Disease Control

    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)

    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.

  36. Duration of Disease Control

    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

    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.

  37. Time to Progression

    Time frame: 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.

  38. Progression-free Survival Time

    Time frame: 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.

  39. Anti-drug Antibody Titers

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

  40. Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC)

    Time frame: 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.

  41. Percentage of Participants With EGFR Amplification Using Fluorescent in Situ Hybridization (FISH) Method.

    Time frame: Week 1 (pre-dose) and Week 4.

Sponsors and collaborators

Lead sponsor

Merck KGaA, Darmstadt, Germany

Industry

Registry information

Official study title

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

Important dates

Study start
2013
Primary completion
2015
Study completion
2015
First posted
Oct 7, 2013
Registry last updated
Aug 23, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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