Phase I/II Study of KRN330 Plus Irinotecan in Patients With Metastatic Colorectal Cancer

Phase II portion is an open-label, single arm study. Based on the results of the Phase I
portion, weekly KRN330 (0.5 mg/kg) and biweekly irinotecan (180 mg/m2) will be used in the
Phase II portion. To be eligible for the Phase II portion, a patient will have recurred or
progressed within 6 months of the last cycle of FOLFOX/CapOx +/- bevacizumab (first-line or
adjuvant regimen for metastatic colorectal cancer). Patients will continue the treatment
until disease progression.

Per protocol, the decision was made to terminate the study based on interim analysis
results. The Response Rate in Phase II did not meet the protocol-specified RR of 15% when
0.5 mg/kg KRN330 was administered weekly in combination with irinotecan(180 mg/m2)biweekly.

Inclusion Criteria:

- Have histologically confirmed colorectal cancer that is metastatic with measurable
disease.

- For the Phase II portion: Have recurred or progressed within 6 months of the last
cycle of FOLFOX +/- bevacizumab first-line or adjuvant regimen for metastatic
colorectal cancer. Note: Those who had initiated FOLFOX/CapOx but stopped oxaliplatin
because of intolerable toxicity are also eligible.

- At least 4 weeks have elapsed since the last chemotherapy, radiotherapy,
immunotherapy, or biologic therapy prior to enrollment (except at least 6 weeks in
the case of nitrosourea and mitomycin).

- Have not received any other investigational agents within 4 weeks of study entry and
have fully recovered from any adverse event due to prior therapy.

- At least 4 weeks have elapsed since any major surgery.

- Have ECOG performance status of 0, 1, or 2.

- Have adequate bone marrow and organ function

Exclusion Criteria:

- Have an active, uncontrolled infection.

- Have known HIV positive status.

- Have known or suspected cerebral metastasis.

- Have had a myocardial infarction (MI) or cerebrovascular accident (CVA) within the
last 6 months; or meet the criteria for AHA class III or IV congestive heart failure
(CHF).

- Have a medical condition requiring chronic use of high-dose corticosteroids or other
chronic immunosuppressive therapy (e.g. methotrexate, azathioprine).

- Have a history of greater than or equal to Grade 2 allergic reaction or
hypersensitivity following exposure to humanized or human monoclonal antibodies (but
not chimeric antibodies).

- Pregnant or breastfeeding women and male or female patients who do not agree to use
effective contraceptive method(s) during the study.