This is a Phase 2, open-label, randomized, 3-arm trial investigating the efficacy of two
Sym004 doses (Arm A and Arm B) compared with a control group (Arm C) in subjects with
metastatic colorectal cancer (mCRC) and acquired resistance to anti-epidermal growth factor
receptor (EGFR) monoclonal antibodies (mAbs).
This trial assesses the efficacy of two different weekly dosing regimens of Sym004 (Arm A: 12
mg/kg/week versus Arm B: 9 mg/kg loading dose followed by 6 mg/kg/week) compared with
investigator's choice in terms of overall survival time in subjects with mCRC. Subjects
assigned to Arm C will receive best supportive care (BSC), Fluorouracil (5-FU), or
Capecitabine, per local standard of care.
Subjects will receive treatment until unacceptable toxicity, disease progression, withdrawal
of consent, or until the subject meets any of the criteria for treatment discontinuation or
trial discontinuation. Therefore, the duration of treatment will differ among individuals and
cannot be fixed in advance.
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, Kirsten rat sarcoma
wild-type (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 RECIST
- Life expectancy of at least 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
- Other protocol defined inclusion criteria could apply
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 AEs (CTCAE) Grade greater than 1 from
previous anti-EGFR therapy at time of randomization
- Magnesium less than 0.9 milligram per deciliter (mg/dL)
- Known hypersensitivity to any of the treatment ingredients. Known previous Grade 3-4
infusion related reactions with anti-EGFR mABs
- Other protocol defined exclusion criteria could apply