Sym004 vs Standard of Care in Subjects With Metastatic Colorectal Cancer

This trial assesses the efficacy of 2 different weekly dosing regimens of Sym004 (Arm A: 9
mg/kg loading dose followed by 6 mg/kg/week dose versus Arm B: 12 mg/kg/week) compared with
investigator's choice in terms of overall survival time in subjects with mCRC. Subjects
assigned to investigator's choice (Arm C) will receive: best supportive care (BSC), or
Fluorouracil (5-FU), or capecitabine, per local standard of care.

The subject will receive weekly Sym004 administration by intravenous (IV) infusion from Week
1 until unacceptable toxicity, disease progression, or consent withdrawal occurs, 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