A Phase I Dose Escalation Study of JX-594 (Thymidine Kinase-deleted Vaccinia Virus Plus GM-CSF) Administered by Intravenous Infusion in Patients With Refractory Solid Tumors

Inclusion Criteria:

- Histologically-confirmed, advanced/metastatic solid tumor refractory to standard
therapy or the patient has refused or does not tolerate the standard therapy; tumors
may include malignant melanoma, non-small cell lung cancer, renal cell carcinoma, and
squamous cell carcinoma of the head and neck

- At least one measurable tumor mass by CT/MRI (i.e. lesion that can accurately be
measured in at least one dimension with longest diameter > 1 cm)

- At least one tumor mass amenable to biopsy and/or FNA

- Expected survival for approximately 16 weeks or longer

- Karnofsky Performance Score (KPS) ≥ 70

- Age ≥18 years

- WBC ≥ 3,500 cells/mm3 and ≤ 50,000 cells/mm3

- ANC ≥ 1,500 cells/mm3

- Hemoglobin ≥ 10 g/dL

- Platelet count ≥ 100,000 plts/mm3

- Total bilirubin ≤ 1.5 x ULN

- AST, ALT ≤ 2.5 x ULN

- Serum chemistries within normal limits (WNL) or Grade 1 - If patients are diabetic or
have a screening random glucose > 160 mg/dL, a fasting glucose must be done and
patients must be WNL or Grade 1 in order to be eligible for the study.

- Acceptable coagulation status: INR ≤ (ULN + 10%)

- CD4 count ≥ 500/mm3

Exclusion Criteria:

- Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or
medication (e.g. systemic corticosteroids)

- Known myeloproliferative disorders requiring systemic therapy

- History of exfoliative skin condition (e.g. eczema or ectopic dermatitis) requiring
systemic therapy

- Tumor(s) invading a major vascular structure (e.g. carotid artery)

- Tumor(s) in location that would potentially result in significant clinical adverse
effects if post-treatment tumor swelling were to occur (e.g. tumors impinging on the
upper airway or affecting biliary tract drainage, etc.)

- Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or
pleural effusions

- Severe or unstable cardiac disease

- Current, known CNS malignancy (history of completely resected or irradiated brain
metastases allowed)

- Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case
of mitomycin C or nitrosoureas)

- Use of anti-viral, anti-platelet, or anti-coagulation medication [Patients who
discontinue such medications within 7 days prior to first treatment may be eligible
for this study.]

- Pulse oximetry O2 saturation <90% at rest

- Experienced a severe systemic reaction or side-effect as a result of a previous
smallpox vaccination

Household contact exclusions:

- Women who are pregnant or nursing an infant

- Children < 5 years old

- History of exfoliative skin condition (e.g. eczema) that at some stage has required
systemic therapy

- Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or
medication (e.g. systemic corticosteroids)