In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol®

Hiltonol® will be administered by intratumoral injection into injectable cutaneous,
subcutaneous and nodal tumors with or without image ultra sound guidance. Visceral organ
metastases will not be injected.

Cycle 1 (weeks 1-13): One readily accessible tumor site (e.g., mucosal, SC or submucosal, or
cutaneous lymph node) will be targeted for injection. The patient will remain in clinic for
monitoring for 1 hour following each of the first two IT injections. Any patient who has a
significant reaction to an IT injection will be observed for 2 hours following all subsequent
IT injections. The target lesion will be biopsied within 7 days prior to the first injection.
If an additional lesion is easily accessible this will also be biopsied.

Study subjects will receive 3 Intra-tumoral (IT) injections of 1.0 mg (0.5 ml) poly-ICLC into
the same lesion on Cycle 1 Week 1 D1, D3, and D5. A dosing range of 7 days is allowed. Cycle
weeks may be shifted as a result of treatment adjustments. One readily accessible tumor site
(e.g. cutaneous, mucosal, SC or submucosal) will be targeted for each cycle of intra-tumoral
injections of poly-ICLC. Study subjects will remain in clinic for monitoring for 1 hour after
each of the first two IT injections. If any patient has a significant reaction to the IT
injection he or she will remain in clinic for 2-hour post injection observations for all
subsequent IT injections. All 3 injections should be given before Week 2 unless there is an
adjustment to a subject's treatment schedule. No more than one injection may be given on a
single day. Treatment adjustments may be the result of unusual circumstances such as
conditions impeding travel, toxicities, a subject's health status requiring medical
intervention outside the purview of study treatment, or the like.

On weeks 2-13 study subjects will then receive booster injections of 1.0 mg (0.5 ml) IM
Poly-ICLC twice weekly at an interval of 48-72 hours between the two injections. These
injections may be administered either in the clinic or at home by the study subjects or the
study subjects' person of choice (e.g., family member, friend). Study subjects who elect the
at home administration option will be given a set of written instructions to follow, and a
diary sheet that they are required to maintain showing when the dates and times injections
were given and the injection sites (extremities). For consistency, study subjects will be
instructed to allow an interval of 48-72 hours between the two injections. IM injections will
be performed using standard technique. Injection site may be rotated based on study subjects'
and investigator preference and will be recorded in the diary. The study nurse will train the
study subjects, or the study subjects' person of choice, on how to inject IM Poly-ICLC for
those study subjects who want the option of home treatment. The first injection will be
administered in clinic under the supervision of study clinical staff and the patient will be
monitored for at least 30 minutes after the first IM injection including a determination of
blood pressure, heart rate, and respiratory rate before and after injection.

The investigational pharmacy will follow its standard operating procedures (SOPs) when
dispensing the study drug for distribution to the study subjects. Study subjects will be
instructed to select the day for that week's first administration of Poly-ICLC and to
administer (or have their person of choice administer) the second injection between 2 and 3
days following the first injection. The clinical staff will provide study subjects with a
sufficient supply of Poly-ICLC, sterile syringes with needles and alcohol swabs for this
purpose.

The study subjects will also be provided with a diary wherein the date, time and injection
site of the study drug is to be noted as well as comments on any side effects. The diary will
be reviewed by the clinic staff with the study subject at clinic visits and collected from
the study subject at the following study visit. Study subjects and/or their person of choice
will be instructed to allow a 48-72 hour interval between the two injections, and that it is
anticipated that the two injections will be given during the course of each 7 day period
starting on Week 3 through week 13. Study subjects will be given the option to receive IM
injections in the clinic if they prefer.

Cycle 2 (weeks 14-26): One readily accessible tumor site (e.g. cutaneous, mucosal, SC or
submucosal) will be targeted for injection. Study subjects will receive 3 Intra-tumoral (IT)
injections of 1.0 mg (0.5 ml) poly-ICLC into the same lesion on Week 14 D1, D3, and D5. A
dosing range of 7 days is allowed. Cycle weeks may be shifted as a result of treatment
adjustments. No more than one injection is given on the same day and all injections are
completed before Week 15 (or week 16 if study treatments are adjusted). A second biopsy of
target lesion will be performed prior to, or within 7 days of the last IT injection in cycle
2. If there is another easily accessible lesion, a non-targeted/non-injected index lesion
will also be biopsied within 7 days following the last IT injection of cycle 2. A third
biopsy will be taken at week 26.

The second cycle may target the same or a different metastatic site at the discretion of the
investigator, but only one lesion will be injected for a given cycle.

In cycle 2, IM injections will be given biweekly on weeks 15-25. The first IM injection for
cycle 2 may be given by the study subjects or study subjects' person of choice at home;
however, it may be given in the clinic at the study subject's preference.

Tumor Assessment: During week 26, tumor assessments will be performed

Follow up Period:

After completion of study treatment, study subjects may be contacted by telephone twice
yearly for up to 36 months to inquire on their health status (e.g., alive, remission,
progressive disease, on new cancer treatment). Study subjects with an initial tumor response
but then long-term recurrence during the follow up period may be offered additional cycles of
treatment depending on the study subject's health status, costs and/or drug availability.

Inclusion Criteria:

1. Histologically confirmed diagnosis of one of the following:

- Melanoma

- Squamous head and neck cancer

- Sarcoma

- Non-Melanoma skin cancers

2. Sarcoma Patients must be 14 years of age or older. All other patients must be 18 years
of age or older.

3. Unresectable disease. Patients with resectable disease may be enrolled after having
refused surgery after a documented consultation with a surgeon.

4. Radiologically or visually measurable recurrent or metastatic disease that is
measurable and at least 10mm in longest dimension.

5. At least one accessible primary or metastatic tumor site that can be readily injected
IT with poly-ICLC with or without ultrasound guidance. This lesion can be superficial
cutaneous, subcutaneous or within a readily accessible lymph node and must measure at
least 10 mm in longest dimension.

6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

7. Acceptable hematologic, renal and liver function as follows:

- Absolute neutrophil count > 1000/mm3,

- Platelets > 50,000/mm3,

- Creatinine ≤ 2.5 mg/dl,

- Total bilirubin ≤ 1.5mg/dl,

- Transaminases ≤ 2 times above the upper limits of the institutional normal, -
INR<2 (international normalized ratio) if off of anticoagulation. Patients on
anticoagulation therapy with an INR>2 may be enrolled at the discretion of the
investigator if they have not had any episodes of severe hemorrhage and if the
site to be injected is not located in the oropharynx or another area where
achieving homeostasis would be complicated by local anatomy.

8. Patients must be able to provide informed consent.

9. Patients with the potential for pregnancy or impregnating their partner must agree to
follow acceptable birth control methods to avoid conception. Contraception must be
continued for at least 2 months following the last dose of poly-ICLC. Women of
childbearing potential must have a negative pregnancy test. While animal reproductive
studies have been negative, the simulated viral infection and anti-proliferative
activity of this experimental drug may theoretically affect the developing fetus or
nursing infant.

Exclusion Criteria:

1. Serious concurrent infection or medical illness, which would jeopardize the ability of
the patient to receive the treatment outlined in this protocol with reasonable safety.

2. Bulky intracranial metastatic disease with shift of midline structures or progressive
brain metastasis such that ongoing therapy for these brain metastasis is required at
the time of enrollment.

3. In the opinion of the local PI: Head and neck cancer patients with airway tumor
recurrence that may compromise breathing or swallowing if inflammation or edema is
transiently aggravated by Hiltonol injection. Head and neck cancer patients with tumor
invading major blood vessels for whom there may be a risk of blockage or bleeding if
inflammation or edema is transiently increased by Hiltonol injections.

4. AIDS defined as a CD4 (cluster of differentiation 4) count less then 200 in the
context of HIV sero-positivity or chronically is taking immunosuppressive medication
such as steroids or transplant related medications.

5. Life expectancy of less than 6 months in the judgment of the study physician.

6. Persistent toxicity from recent therapy that has not sufficiently resolved in the
judgment of the study physician.

7. History of active immunotherapy in the previous month.