A Study to Assess PV-10 Chemoablation of Cancer of the Liver

Subject will be enrolled in one of four planned cohorts (Main Study Group, Expansion Cohort
1, Expansion Cohort 2 or Expansion Cohort 3).

Main Study Group. Three initial subjects with either HCC or cancer metastatic to the liver
will receive 0.25 mL PV-10 per cc lesion volume (Lv) to a single lesion (up to a maximum dose
of 7.5 mL PV-10). If none of the initial three subjects experiences a new and persistent
CTCAE Grade 3 or greater non-hematological or any Grade 4 hematological toxicity over a
28-day follow-up interval, an additional three subjects will be enrolled and similarly
treated with PV-10 administered at 0.50 mL per cc Lv (up to a maximum dose of 15 mL PV-10)
provided no new and persistent Grade 3 or greater non-hematological or any Grade 4
hematological toxicity occurs.

Expansion Cohort 1 (EC1: PV-10 plus/minus Checkpoint Inhibition). Following demonstration of
safety and tolerability in the Main Study Group, up to 48 additional subjects with cancers
metastatic to the liver or with HCC will be enrolled into Expansion Cohort 1 (EC1). Subjects
will be treated with PV-10 administered at 0.50 mL per cc Lv (up to a maximum dose of 15 mL
PV-10). Subjects may receive injection of up to two lesions in any PV-10 treatment cycle.
Enrollment will continue provided no new and persistent Grade 3 or greater non-hematological
(excluding fatigue) or any Grade 4 hematological toxicity occurs.

Expansion Cohort 2 (EC2: PV-10 plus Checkpoint Inhibition). Following demonstration of safety
and tolerability in the Main Study Group, up to 12 additional subjects with HCC on a
background of standard care checkpoint inhibition therapy (i.e., anti-PD-1 therapy) will be
enrolled into Expansion Cohort 2 (EC2). Subjects will be treated with PV-10 administered at
0.50 mL per cc Lv (up to a maximum dose of 15 mL PV-10). Subjects may receive injection of up
to two lesions in any PV-10 treatment cycle. Enrollment will continue provided no new and
persistent Grade 3 or greater non-hematological (excluding fatigue) or any Grade 4
hematological toxicity occurs.

Expansion Cohort 3 (EC3: PV-10 plus Checkpoint Inhibition). Following demonstration of safety
and tolerability in the Main Study Group, up to 12 additional subjects with hepatic
metastases of uveal melanoma (mUM) on a background of standard care checkpoint inhibition
therapy (i.e., anti-CTLA-4, anti-PD-1 or combination anti-CTLA-4 and anti-PD-1 therapy) will
be enrolled into Expansion Cohort 3 (EC3). Subjects will be treated with PV-10 administered
at 0.50 mL per cc Lv (up to a maximum dose of 15 mL PV-10). Subjects may receive injection of
up to two lesions in any PV-10 treatment cycle. Enrollment will continue provided no new and
persistent Grade 3 or greater non-hematological (excluding fatigue) or any Grade 4
hematological toxicity occurs.

Concomitant therapy with immune checkpoint inhibition is allowed in Expansion Cohort 1 and
required in Expansion Cohort 2 and Expansion Cohort 3. This concomitant therapy must commence
at least 7 days prior to initial PV-10 administration.

Subjects in each Expansion Cohort one or more additional injectable tumor ≥ 1 cm in diameter
will be eligible for treatment of one or more additional injectable tumor 28 days to 6 months
after prior PV-10 administration provided that any prior treatments with PV-10 were well
tolerated. This may be repeated until all injectable tumors ≥ 1 cm in diameter have received
PV-10.

Inclusion Criteria:

- Age 18 years or older, males and females.

- Histologically or cytologically confirmed, or clinically diagnosed based on currently
accepted standards, cancer metastatic to the liver or HCC that is not amenable at the
time of enrollment to resection, transplant or other potentially curative therapy.

- At least one Target Lesion determined to be amenable to percutaneous injection by the
treating physician.

- Target Lesion(s) must have measurable disease, defined as a unidimensionally
measurable lesion ≥ 1.0 cm in longest diameter by helical CT; the maximum diameter of
Target Lesion(s) shall be ≤ 4.9 cm.

- Performance status of Karnofsky scale 60%-100% or ECOG performance scale 0-2.

- Life expectancy ≥ 12 weeks.

- Hematopoietic Function: WBC ≥ 2,500/mm3; ANC ≥ 1000/mm3; Hemoglobin ≥ 8 g/dL; Platelet
count ≥ 50,000/mm3; Coagulation: INR ≤ 1.3.

- AST and ALT < 5 times ULN; ALP < 5 times ULN; Bilirubin ≤ 1.5 times ULN; Creatinine ≤
1.5 times ULN and eGFR ≥ 50.

- Thyroid Function: Total T3 or free T3, total T4 or free T4 and THS ≤ CTCAE Grade 2
abnormality.

- Renal Function: Adequate renal function in the opinion of the Investigator with no
clinically significant renal impairment or uncontrolled renal disease.

- Cardiovascular Function: Adequate cardiovascular function in the opinion of the
Investigator with no clinically significant uncontrolled cardiovascular disease.

- Respiratory Function: Adequate respiratory function in the opinion of the Investigator
with no clinically significant uncontrolled respiratory disease.

- Immunological Function: Adequate immune system function in the opinion of the
Investigator with no known immunodeficiency disease.

- Informed Consent: Signed by the subject prior to screening.

Exclusion Criteria:

- Target Lesion(s) must not be contiguous with, encompass or infiltrate major blood
vessels.

- Primary HCC amenable to resection, transplant or other potentially curative therapy.

- Surgery: Subjects who have received hepatic surgery, ablation or chemoembolization
within 4 weeks of PV-10 administration.

- Radiation Therapy: Hepatic radiation within 4 weeks of PV-10 administration.

- Chemotherapy: Chemotherapy within 4 weeks of PV-10 administration (6 weeks for
nitrosoureas or mitomycin C).

- Investigational Agents: Investigational agents within 4 weeks (or 5 half-lives) of
PV-10 administration.

- Phototoxic or Photosensitizing Agents: Concomitant agents posing a clinically
significant risk of photosensitivity reaction within 5 half-lives of PV-10
administration.

- Concurrent or Intercurrent Illness: Impaired wound healing due to diabetes;
Significant concurrent or intercurrent illness, psychiatric disorders or alcohol or
chemical dependence that would compromise Subject safety or compliance or interfere
with interpretation of the study; Uncontrolled thyroid disease or cystic fibrosis;
Presence of clinically significant acute or unstable cardiovascular, cerebrovascular
(stroke), renal, gastrointestinal, pulmonary, immunological (with the exception of the
presence of hepatitis B virus (HBV), viral hepatitis, or cirrhosis), endocrine, or
central nervous system disorders; Current encephalopathy or current treatment for
encephalopathy; Variceal bleeding requiring hospitalization or transfusion within 4
months of screening; History of human immunodeficiency virus or acquired immune
deficiency syndrome; The clinical presence of ascites.

- Pregnancy: Female subjects who are pregnant, lactating or have positive serum β HCG
pregnancy test taken within 7 days of PV-10 administration; Fertile subjects who are
not using effective contraception (e.g., oral contraceptives, intrauterine devices,
double barrier methods such as condoms and diaphragms, abstinence or equivalent
measures).