IMCgp100 in Advanced Unresectable Melanoma

This study will test the safety effect of a single dose of the investigational drug IMCgp100
when administered directly into the metastatic melanoma lesion in patients with advanced
metastatic melanoma. IMCgp100 is a drug made up of two components. The first is the T cell
receptor designed to bind specifically and tightly with protein found at high levels on the
surface of melanoma cancer cells and second is an anti-CD3 fragment that is meant to bind to
and activate the T cells. There will be two stage dose regimens each enrolling 3 patients.
Stage 1 dose will 0.00017 mg IMCgp100 and Stage 2 dose will be 0.0017 mg IMCgp100. Inclusion
Criteria: 1. Histologically confirmed dx of advanced unresectable melanoma not requiring
immediate treatment and/or in a window between treatments 2. Two or more cutaneous or
subcutaneous melanoma metastatic lesions 7 to 15 mm in at least one dimension and amenable
to subsequent biopsy 3. Greater or equal to 18 years of age 4. ECOG PS 0-2 5.

Able to provide informed consent and willing to comply with protocol requirements 6. Female
patients must not be of childbearing potential or must have negative serum pregnancy test 48
hours prior to receiving investigational drug 7. Male patients must agree to use reliable
form of birth control throughout study 8. Must have adequate organ system function Exclusion
Criteria: 1. Received any other chemo, immune, radiation or investigational therapy agents
within 2 weeks prior to study treatment 2. Cutaneous metastasis that have received prior
local therapy 3. Pregnant or breastfeeding 4.

History of autoimmune disease 5. Current treatment with steroid or other immunosuppresive
meds 6. Active uncontrolled infection 7. Known HIV infection 8. Uncontrolled seizures 9.
Known delayed wound healing 10. On full dose anticoagulation therapy.

Inclusion Criteria:

- 1. Histologically confirmed diagnosis of melanoma, with advanced unresectable disease
not currently requiring immediate treatment and/or in a window between treatments.

- 2. Two or more cutaneous or subcutaneous melanoma metastatic lesions 7-15 mm in at
least one dimension and amenable to subsequent biopsy.

- 3. Age 18 years

- 4. ECOG performance status 0-2

- 5. Able to understand and to provide written informed consent and willingness to
comply with all protocol requirements;

- 6. Female patients who are not be of childbearing potential as documented by medical
history (e.g., tubal ligation or hysterectomy), or be post menopausal with a minimum
1 year without menses or have a negative serum beta human chorionic gonadotropin
(HGC) pregnancy test within 48 hours prior to receiving the intratumoral injection
and agree to use an acceptable form of birth control, defined as abstinence or use of
an intrauterine device (IUD), oral contraceptive, barrier and spermicide, or hormonal
implant throughout the study period;

- 7. Male patients who must agree to use an acceptable form of birth control throughout
the study period.

- 8. Adequate organ system function as evidenced by laboratory values: -Absolute
neutrophil count (ANC) greater than or equal to 1.0 X 109/L -Hemoglobin greater than
or equal to 9 g/dL -Platelets greater than or equal to 75 X 109/L -Total bilirubin
less than or equal to 1.5 mg/dL -AST and ALT less than or equal to 2.5 X ULN ( 2.5 X
ULN in the presence of liver metastasis.) -Creatinine less than or equal to 2 mg/dL
-TSH within normal limits -INR/PT and PTT less than or equal to 1.3 X ULN

Exclusion Criteria:

- 1. Receive any chemotherapy, immunotherapy, radiation therapy, or other
investigational agents (agents part of a research protocol or not approved by the
FDA) within 2 weeks prior to injection. A minimum of 14 days is required between last
therapy and injection on this study. In addition, any clinically significant
drug-related toxicity should have recovered to grade 1 or less (excluding alopecia)

- 2. Patients without cutaneous or subcutaneous metastatic lesions;

- 3. Cutaneous metastases that have received prior local therapy, such as radiation or
isolated limb perfusion.

- 4. Pregnancy or breastfeeding

- 5. History of autoimmune disease (excluding vitiligo or controlled thyroid disease)
or immunodeficiency.

- 6. Current treatment with steroids (inhaled, topical or systemic) or other
immunosuppressive medications within 2 weeks of injection;

- 7. Active uncontrolled infection;

- 8. Known HIV positivity;

- 9. Uncontrollable seizures;

- 10. Known delayed wound healing;

- 11. Full dose anticoagulation with heparin, warfarin, or any other anticoagulant
within 2 weeks of injection ;

- 12. History of acute coronary syndromes (including unstable angina), coronary
angioplasty, or stenting, stroke or TIA within the past 24 weeks.;

- 13. Known hypersensitivity of IMCgp100 or any of its components (ie, Tween) ;

- 14. Class II, III, or IV heart failure as defined by the New York Heart Association;

- 15. Any psychological, familial, sociological, or geographical conditions that do not
permit compliance with the protocol.

- 16. Any other condition that in the investigators opinion would jeopardize compliance
with the protocol ;