Trial of PalloV-CC in Colon Cancer

This is a single arm, open label, phase Ib trial of neoadjuvant vaccination in colon cancer.
The primary endpoint is the safety and toxicity of the vaccine. The primary immunologic
endpoint is the impact of vaccination on the tumor microenvironment compared to prospectively
evaluated, tissue banked specimens from historical controls. The tumor microenvironment will
also be compared in matched pre- and post-treatment tissue samples in vaccinated subjects.
Subjects with endoscopic biopsy proven colon cancer will be identified by the staff in the
gastroenterology, surgery, and/or the hematology/oncology clinics at the individual study
sites. A research nurse, study coordinator, or study investigator will approach these
subjects about being in the trial and will introduce the trial to the prospective volunteer
subject. If the subject is interested and appears eligible, the nurse, study coordinator, or
investigator will arrange an appointment to counsel and consent the patient. Once consent is
obtained, the nurse, study coordinator, or investigator will thoroughly screen the patient
for inclusion and exclusion eligibility criteria. If volunteers meet all inclusion criteria
and none of the exclusion criteria and agree to participate, they will continue in the study,
consented and enrolled for treatment assignment. Enrollment will start in cohort 1 with
enrollment of 6 patients, and follow sequentially into the remaining cohorts, until all
cohorts are completed. After treatment of all 6 patients in each dose cohort, a comprehensive
safety analysis will be performed for short-term toxicity. If no dose limiting toxicity (DLT,
>grade 2, related, or serious adverse event (SAE)) is found, then the next cohort will be
enrolled. If three patients in a given dose cohort experience a DLT, then that dose will be
determined to be the maximal tolerated dose (MTD), and the next dose cohort will not be
initiated. At the completion of dosing of cohorts (last surgical colectomy performed), a
comprehensive safety analysis will be performed for long-term toxicity. If the MTD is not
reached, then a total of 24 patients will be enrolled.

Treatment cohorts (each n=6, total of n=24):

1. 1 x 108 particles of PalloV-CC

2. 2 x 108 particles of PalloV-CC

3. 4 x 108 particles of PalloV-CC

4. 8 x 108 particles of PalloV-CC

PalloV-CC is inoculated weekly via intradermal injection. There will be sequential enrollment
of dose-escalation cohorts (Appendix A), each patient treatment period is 4 weeks (Appendix
B). Patients will conclude treatment with colectomy. Safety data will be collected on local
and systemic toxicities and graded and reported per the Common Terminology Criteria for
Adverse Events (CTCAE) v4.03.

A total of 190 mL of blood will be drawn throughout the course of the study over a 3-4 week
period. The patient will have 70mL of blood drawn for the following: a CBC with differential
(10 mL of blood), a CMP (10 mL of blood), and study blood (50 mL of blood). This will be
drawn on two separate occasions: once prior to the first vaccine inoculation, and again after
the completion of the final vaccine inoculation (but prior to surgery). An additional 50 mL
of study blood will be drawn midway through the vaccine series (at the third inoculation).
Study subjects may opt out of the collection of study blood (150 mL total over three blood
draws).

Inclusion Criteria:

1. Stage I-IV (resectable) colon cancer subjects identified prior to their definitive
surgery

2. Diagnosis definitively confirmed by endoscopic biopsy with tumor tissue slides
available for analysis

3. Asymptomatic and capable of waiting 4 weeks prior to definitive surgery

4. ECOG 0-1 performance

5. Not involved in other clinical trials

6. Capable of giving informed consent

Exclusion Criteria:

1. Symptoms of obstruction or GI bleeding that necessitate more urgent surgical
intervention

2. Cancer not definitively confirmed on endoscopic biopsy (i.e., Only high-grade
dysplasia or adenoma identified, even if malignancy is suspected)

3. Known immune deficiency disease or HIV, active HBV, or active HCV

4. Steroids or other immunosuppressants received within 6 weeks of enrollment

5. Any colon cancer directed treatment (chemotherapy or radiation) received or planned
prior to surgical resection

6. A history of any hematologic malignancy or myeloproliferative disease within 5 years
prior to enrollment

7. Leukopenia or neutropenia within two weeks of presentation

8. ECOG >2

9. Pregnancy (serum or urine HCG) or breast feeding

10. Tbili >1.8, Cr >2, Hgb <10, platelet count <50,000, WBC <2,000