QUILT-3.019: Phase 2 Study of NPC-1C Chimeric Monoclonal Antibody to Treat Pancreatic and Colorectal Cancer

The limitations of many current therapeutic products for pancreatic cancer are widely
recognized. Despite the development of several new treatment regimens for pancreatic cancer,
little if any benefit has been appreciated, leaving this disease as one of the most
significant unmet medical needs in cancer.

NPC-1C is a chimeric immunoglobulin molecule comprised from the variable region of the heavy
chain and light chain of murine NPC-1, genetically engineered in-frame with the constant
regions of a human IgG1 isotype. NPC-1, the predecessor of NPC-1C, was derived from a Tumor
Associated Antigen (TAA) based vaccine that was previously tested in a Phase 1-2 clinical
trial performed in the United States in the 1980's that explored the use of TAA therapy in
patients with adenocarcinoma of the colon. These early studies demonstrated safety as well as
preliminary evidence of activity in these patients treated with the vaccine.

NPC-1C antibody-staining studies demonstrate specific immunoreactivity with cancer tissues
from colon and pancreas patients, whereas only weak binding, if at all, is observed in normal
pancreas or colon tissues with no cross-reactivity observed in other normal human tissues.
The Phase 2 portion of this trial is an open label, multi-center study estimated to treat
approximately 30 patients with pancreatic cancer who have failed first line therapy, and 43
patients with metastatic colorectal cancer who are refractory to standard treatment.

INCLUSION CRITERIA:

- Age: >/= 18

- Diagnosis:

- Histologically confirmed recurrent, locally advanced unresectable or metastatic
adenocarcinoma of the pancreas who have progressed after front line chemotherapy,
OR

- Histologically confirmed metastatic colorectal adenocarcinoma who have progressed
after at least 2 standard chemotherapy regimens.

- Tumor sections must stain >/= 20% positive for NPC-1C antibody/antigen target

- Measurable disease (by RECIST)

- Karnofsky performance status of >/= 50%

- Laboratory Function (within 21 days of receiving first dose of study drug):

- Hemoglobin > 8.5 g/dL, or on stable doses (hematocrit stable within 1 gram and
dose stable for one month) of erythropoietin or similar medication.

- Absolute neutrophil count (ANC) >/= 1,500/mm3

- Platelets >/= 50,000/mm3

- Total bilirubin
- ALT and AST times the ULN

- Creatinine
- Voluntary written informed consent before performance of any study-related procedure
that is not part of normal medical care.

- Expected to be able to remain on a study protocol for at least 8 weeks.

- Is post-menopausal, surgically sterilized, or willing to use acceptable methods of
birth control for the duration of the study. Male subject agrees to use an acceptable
barrier method for contraception during the study.

EXCLUSION CRITERIA:

- Has history of disseminated or uncontrolled brain metastases or central nervous system
disease.

- Ascites with abdominal distention.

- Mechanical, non-reversible reason for not being able to eat, or have a likelihood of
developing malignant bowel obstruction during the course of the induction phase of
treatment; subjects with uncomplicated J-tubes will not be excluded.

- Any major surgery within four weeks of enrollment.

- Uncontrolled concomitant illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
arrhythmia.

- Has another serious medical illness, including a second malignancy, or psychiatric
illness that could, in the Investigator's opinion, potentially interfere with the
completion of treatment according to this protocol.

- Pregnant or breast-feeding.

- Any chemotherapeutic agents or corticosteroids within 2 weeks of study entry or
biologic treatment within 4 weeks of study entry.

- Use of any high risk medications that prolong the QT/QTc interval.

- History of allergic reaction to Erbitux greater than grade 1.

- Uncontrolled diabetes.

- Prior history of a documented hemolytic event.

- Receiving warfarin.