Metastatic colorectal cancer with Acquired Resistance to Anti-EGFR Monoclonal Antibodies MedDRA version: 19.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Sym004
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Futuximab
CAS Number: 1310460-85-5
Current Sponsor code: 992 DS
Other descriptive name: Chimeric IgG anti-EGFR mAb
Sponsors
Symphogen A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Written informed consent obtained before undergoing any study-related activities - Male or female, at least 18 years of age - Subjects with histologically or cytologically confirmed mCRC, KRAS WT at initial diagnosis - Failure of or intolerance to 5-FU, Oxaliplatin, and Irinotecan - Acquired resistance to marketed anti-EGFR mAbs as defined in the protocol - Measurable disease defined as one or more target lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) - Life expectancy of at least 3 months - ECOG performance status = 1 - Other predefined inclusion criteria may apply Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: - Pretreatment with regorafenib - Subjects who in the opinion of the subject and investigator would benefit more from regorafenib treatment (except where regorafenib is not reimbursed in the country) - Skin rash Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1 from previous anti-EGFR therapy at time of randomization - Magnesium < 0.9mg/dL - Known hypersensitivity to any of the treatment ingredients. Known previous Grade 3-4 infusion related reactions with anti-EGFR mABs - Other predefined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - To assess the efficacy of the 2 different weekly dosing regimens of Sym004 in subjects with mCRC in terms of best overall response and progression-free survival time and time to treatment failure; - To determine the safety profile of the 2 different weekly dosing regimens; - To evaluate the dose intensity for the 2 different weekly dosing regimens; - To determine the pharmacokinetic (PK) profile; - To evaluate the occurrence of antidrug antibody (ADA); - To identify potential predictive biomarkers of response to treatment including but not limited to RAS pathway mutations, HER2 and MET status, EGFR and HER3 ligands plasma protein levels; tumor localization; - To evaluate quality of life;Main Objective: To assess the efficacy of 2 different weekly dosing regimens (9 mg/kg loading dose followed by 6 mg/kg/week dose versus 12 mg/kg/week) of Sym004 compared with investigator`s choice in terms of overall survival time in subjects with metastatic colorectal cancer (mCRC).;Primary end point(s): The primary endpoint is overall survival (OS);Timepoint(s) of evaluation of this end point: OS will be evaluated when 181 events of randomized patients are reported; expected in 2.5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Best overall response according to RECIST v1.1 - Progression-free survival time - Time to treatment failure - number of subjects with AEs, serious AEs, treatment emergent AEs, AEs leading to death, and AEs with Grade >= 3 NCI-CTCAE (V.4.03) - Relative dose intensity - Pharmacokinetic profile (area under curve AUC 0-t, half-life, clearance, volume of distribution, C max, C trough, t max) - Host immune response, number of subjects with anti-drug antibodies (ADA) - Biomarkers: including but not limited to RAS pathway mutations, HER2 and MET status, EGFR and HER3 ligand levels - Quality of life by subject reporting questionnaires using EORTC QLQ-C30 (version 3) - Quality of life by subject reporting questionnaires using EORTC QLQ-CR29 - Quality of life by subject reporting questionnaires using FACT-EGFR18;Timepoint(s) of evaluation of this end point: Efficacy endpoints: - from randomization until first event, where an event can be a progression [radiologically confirmed or clinical progression] or death due to any cause, where death will only be considered as an event if it occurs within 12 weeks after last tumor response assessment without progression Biomarkers: - as defined in the protocol Pharmacokinetics: - as defined in the protocol Quality of life: - every 3/6 weeks during the Treatment Period Safety endpoints: - until 28 days after the last IMP administration or up to 21 months | — |
Countries
Austria, Belgium, France, Germany, Hungary, Italy, Poland, Russian Federation, Spain, United States
Contacts
Public ContactIvan Horak
Symphogen A/S
Outcome results
None listed