Inclusion Criteria:

- Patients must meet all of the following criteria to be eligible for enrollment in the
study.

1. Histologically confirmed CRC adenocarcinoma that is metastatic or locally
recurrent CRC that is nonresectable

2. Patients must agree to genetic testing of the original or metastatic CRC tumor
biopsy tissue for K-RAS mutational status.

3. Disease progression

4. Previous therapy with irinotecan, oxaliplatin, and fluoropyrimidine either alone
or in any combination(s). Patients must have radiographically documented
progressive disease while receiving, or within 3 months of receiving, these
agents alone or in combination.

5. No more than 2 prior cytotoxic chemotherapy regimens.

6. Age 18 years or older

7. Measurable disease by RECIST Version 1.1

8. ECOG performance status of 0 or 1

9. Adequate bone marrow, renal, and hepatic function

Exclusion Criteria:

- Patients meeting any of the following exclusion criteria will not be eligible for
enrollment.

1. Known chronic infectious disease

2. Major surgery within 3 weeks before study start

3. Known or suspected brain metastases requiring intervention with steroids and/or
radiation therapy.

4. Prior chemotherapy, immunotherapy, non-investigational agent, or other therapy
used to treat the cancer within 3 weeks before the scheduled administration of
EZN-2208

5. History of other primary cancer within 5 years of enrollment, unless

1. Curatively resected non-melanomatous skin cancer, or

2. Curatively resected cervical cancer

6. Lack of recovery to Grade 1 from any reversible side effects related to the
administration of an investigational agent, or other prior treatments for the
cancer

7. Any condition such as uncontrollable diabetes, uncontrollable hypertension, or
active infection.

8. Current participation in another clinical study with an investigational agent
and/or use of an investigational drug (not including investigational use of an
approved drug) in the 30 days before the first administration of EZN-2208