Study of Combined SGT-53 Plus Gemcitabine/Nab-Paclitaxel for Metastatic Pancreatic Cancer

The p53 is a vital human tumor suppressor gene. Loss of p53 suppressor function is present in
the majority of human cancers. The p53 protein has a diverse range of functions including
regulation of cell cycle checkpoints, cell death (apoptosis), senescence, DNA repair,
maintenance of genomic integrity, and control of angiogenesis. Abnormalities of the p53 gene
may impact the efficacy of standard anticancer treatments such as radiation and chemotherapy.
P53 mutation and pathway dysfunction are associated with poor clinical outcomes and the
presence of the p53 mutation correlates with resistance to chemotherapy and radiation. The
development of somatic gene therapy has created the potential to restore wild type function
of p53. SGT-53 is a complex of cationic liposome encapsulating a normal human wild type p53
DNA sequence in a plasmid backbone. This complex has been shown to efficiently and
specifically deliver the p53 cDNA to the tumor cells. Introduction of the p53 cDNA sequence
is expected to restore wtp53 function in the apoptotic pathway. P53 restoration has been
shown most effective in enhancing cytotoxicity in combination with an agent which results in
DNA damage or initiates apoptosis. This is a Phase II clinical trial of SGT-53 plus the
recently approved chemotherapeutic combination of gemcitabine/Abraxane® (nab-paclitaxel) as a
first-line therapy in patients with confirmed metastatic pancreatic cancer. In addition to
determining Progression Free Survival at 5.5 months (PFS5.5mos), this trial will evaluate the
response rate, overall survival and time to progression as well as the tolerability and
safety of SGT-53 in combination with gemcitabine/nab-paclitaxel.

Inclusion Criteria:

- Patients with histologic or cytologic diagnosis of stage IV metastatic pancreatic
adenocarcinoma.

- One or more tumors measurable on CT scan.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

- Life expectancy of at least 3 months.

- Age ≥ 18 years.

- Signed, written IRB-approved informed consent.

- A negative pregnancy test (if female and of child-bearing potential).

- Acceptable liver function:

- Bilirubin ≤ 1.5 times upper limit of normal

- AST (SGOT), ALT (SGPT) ≤ 2.5 x ULN

- Serum creatinine ≤ 1.5 X ULN

- Acceptable hematologic status:

- Absolute neutrophil count ≥ 1500 cells/mm³

- Platelet count ≥ 100,000 (plt/mm³)

- Hemoglobin ≥ 10 g/dL

- Acceptable blood sugar control

*Fasting glucose value ≤ 160 mg/dL

- Urinalysis: No clinically significant abnormalities.

- PT and PTT ≤ 1.5 X ULN

- For men and women of child-producing potential, willingness to use of effective
contraceptive methods during the study.

- NOT have received any prior cytotoxic chemotherapy or investigational therapy.
However, this study may be used as 2nd line treatment of patients who progressed on or
were intolerant of 1st line FOLFIRINOX. Prior treatment with gemcitabine administered
as radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months
have elapsed since completion of the last dose and no lingering toxicities are
present.

- They also must NOT have received chemotherapy, radiotherapy, surgery or
investigational therapy for the treatment of metastatic disease.

- Organ function characterized by ≤ Grade 1.

Exclusion Criteria:

- Patient has received any prior cytotoxic chemotherapy for pancreatic cancer with the
exception of patients who progressed on or were intolerant of 1st line FOLFIRINOX.
Prior treatment with gemcitabine administered as a radiation sensitizer in the
adjuvant setting is allowed, provided at least 6 months have elapsed since completion
of the last dose and no lingering toxicities are present. Patients who previously had
and were treated with standard therapy for non-pancreatic cancer will be evaluated for
entry into the trial on a case-by-case basis.

- New York Heart Association Class III or IV, cardiac disease, myocardial infarction
within the past 6 months, unstable arrhythmia, unstable angina (chest pain greater
than three times weekly while on therapy), evidence of ischemia on ECG, or abnormal
stress echocardiogram with evidence of ischemia, or LVEF < 50%.

- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy.

- Treated with antibiotics for infection within one week prior to study entry.

- Fever (> 38.1°C)

- Have hematological malignancy

- Have diastolic blood pressure of > 90 mm Hg resting at baseline despite medication.

- Pregnant or nursing women.

- Treatment with surgery, or investigational therapy within 28 days prior to study entry
or radiation therapy within 6 months prior to study entry.

- Have received chemotherapy, radiotherapy, surgery or investigational therapy for the
treatment of metastatic disease.

- Unwillingness or inability to comply with procedures required in this protocol.

- Known infection with HIV, Hepatitis B, or Hepatitis C.

- Serious nonmalignant disease that could compromise protocol objectives in the opinion
of the Investigator and/or the Sponsor.

- Patients who are currently receiving any other investigational agent.

- Patients who are currently taking Coumadin or Coumadin derivatives other than to
maintain patency of venous access lines.

- Receiving systemic steroids or other chronic immunosuppressive medications within 30
days prior to study entry

- Receiving hematopoietic growth factors

- Had within six months prior to enrollment any of the following:

- Cerebrovascular accident

- Uncontrolled congestive heart failure

- Have significant baseline neuropathies

- Requires renal dialysis

- Had prior exposure to gene vector delivery products