A Phase 1, Open Label, Dose Finding Study to Assess the Safety and Tolerability of IMCgp100, a Monoclonal T Cell Receptor Anti-CD3 scFv Fusion Protein in Patients With Advanced Malignant Melanoma

Inclusion Criteria:

1. Pathologically documented Stage IV malignant melanoma or unresectable Stage III
melanoma for which no standard effective therapy exists or for which an appropriate
window exists between alternative therapeutic options. Patients for whom early
treatment with vemurafenib is indicated e.g. rapidly progressing or symptomatic
disease, are excluded from this trial.

2. Previous surgery (other than resection of skin metastases), radiotherapy,
chemotherapy, immunotherapy or experimental therapy completed >4 weeks before and all
adverse events resolved to ≤ grade 1. In cases where localised radiotherapy has been
applied, treatment with IMCgp100 can be commenced after a two week period.

3. HLA A2 positive.

4. ≥ 18 years old.

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

6. For patients in the Dose-Expansion part only, measurable disease according to RECIST
criteria. For patients in the Dose-escalation part of the study, only 'assessable
disease' is required.

7. Life expectancy >3 months.

8. Blood tests within the following parameters:

1. Platelet count ≥100 x 109/L

2. Haemoglobin ≥10g/dL

3. Calculated creatinine clearance ≥60 mL/min using the modified Cockcroft-Gault
equation

4. Neutrophil counts ≥1x109/L

5. Lymphocyte count ≥0.5x109/L

9. Female patients of childbearing potential must use maximally effective birth control
during the period of therapy, must be willing to use contraception for 6 months
following the last study drug infusion and must have a negative urine or serum
pregnancy test upon entry into this study. Otherwise, female patients must be
postmenopausal (no menstrual period for a minimum of 12 months) or surgically
sterile.

10. Male patients must be surgically sterile or willing to use a double barrier
contraception method upon enrolment, during the course of the study, and for 6 months
following the last study drug infusion.

11. Able to give informed consent.

Exclusion Criteria:

1. Symptomatic brain metastases that are unstable, require steroids, or that have
required radiation within the last 28 days

2. Other active malignancy in the past 5 years except carcinoma in situ, completely
excised non-melanomatous skin cancer or any other malignancy that in the opinion of
the investigator is considered to be cured.

3. Comorbid medical condition that would increase the risk of toxicity in the opinion of
the investigator or sponsor. Any symptomatic ongoing infection must be resolved
before the patient can be treated in the study.

4. Uveitis

5. Had myocardial infarction within 1 year before enrolment, symptomatic congestive
heart failure (New York Heart Association >Class II), unstable angina or unstable
cardiac arrhythmia requiring medication.

6. Has an ejection fraction <50%.

7. Clinically significant electrocardiogram (ECG) changes that obscure the ability to
assess the RR, PR and QT intervals. Patients with QTc calculated by Bazetts or
locally preferred formula which is greater than 500ms.

8. Has hepatic function as follows:

1. Aspartate aminotransferase >2.5 x upper limit of normal (ULN)

2. Alanine aminotransferase >2.5 x ULN

3. Bilirubin >2.0 x ULN

4. Prothrombin time or partial thromboplastin time>1.5 x ULN

9. Bleeding diathesis.

10. Immunosuppressive condition or treatment including previous transplantation,
splenectomy or known HIV infection.

11. Has a history of adult seizures.