A Randomized, Multicenter Phase 3 Study to Compare the Efficacy of Panitumumab in Combination with Chemotherapy to the Efficacy of Chemotherapy Alone in Patients with Previously Treated Metastatic Colorectal Cancer

Panitumumab is a high affinity fully human IgG2 mAb directed against human
EGFr. P*mAb blocks the ligands EGF and TGFα binding to EGFr, inhibits tumor
growth, and elicits both tumor regression and eradication of established tumors
in murine xenograft tumor models. 1700 Subjects with cancer have been enrolled
in P*mAb phase 1,2 and 3 studies. P*mAb has been studied as monotherapy in
multiple studies of mCRC and solid tumors. P*mAb has also been studied in
combination with chemotherapy for non-small cell lung cancer and with
chemotherapy and bevacizumab for mCRC.

The primary objective is to evaluate the treatment effect of P*mAb plus
FOLFIRI on overall survival (OS) and progression-free survival (PFS) compared
to FOLFIRI alone as second line therapy for metastatic colorectal cancer.

This is an open label, randomized, multicenter study. Eligible subjects will be
randomized in a 1:1 ratio to second line therapy consisting of either P*mAb
plus FOLFIRI or FOLFIRI alone. Sample size is 1100 subjects (approximately 550
per treatment arm). P*mAb and chemotherapy will be administered in cycles
lasting 14 days, or longer in the event that a cycle is delayed due to
toxicity. Subjects will be permitted to receive P*mAb and/or chemotherapy until
disease progression or unacceptable toxicities. Subjects with evidence of
disease progression will be discontinued from treatment dosing and will be
followed for safety and survival

Subjects will be randomized to receive P*mAb plus FOLFIRI or FOLFIRI alone.
Panitumumab will be supplied at a concentration of 20 mg/ml in 10mL vials. The
product will be diluted in a minimum volume of 100mL pyrogen-free 0.9% sodium
chloride solution, USP/PhEur (saline solution) and infused by an infusion pump
using an in-line filter (0.22 micron) set up.

Upon meeting all eligibility criteria and completing all screening assessments,
subjects will be randomized into one of the two treatment arms. The following
procedures will be performed per the schedule outlined in Appendix A, (page
91-93 of the protocol): medical and medication history, physical exam, vital
signs, ECG, patient reported outcomes, hematology lab, chemistry lab,
immunogenicity testing, serum testing for CEA, biomarker lab, biomarker and
pharmacogenetic analysis on tumor tissues, CT/MRI scans. Adverse events, and
concomitant medications will be recorded throughout study participation.

Mild to moderate skin rash is a very common side effect in patients treated
with Panitumumab. Other very common adverse events include; nausea, loss of
appetite, abdominal pain, constipation, irritation of the mouth, feeling tired,
difficulty sleeping, diarrhea and vomiting, dizziness, muscle aching, joint
pain, back pain, headache, anxiety and fever. During or within a day or two
following the administration of panitumumab, patients may experience infusion
reactions. There is also a possibility patient*s immune system may develop
antibodies against panitumumab.
All possible adverse effects of receiving panitumumab together with FOLFIRI
chemotherapy are still unknown at this time. Patient*s may experience low white
blood cell counts, low red blood cell counts, low platelet counts, mouth sores
or bleeding gums, increased nausea, vomiting, loss of appetite, weight loss,
diarrhea or tiredness.