Evaluation of a New Vaccine Treatment for Patients With Metastatic Skin Cancer

Study of GSK2302025A Antigen-Specific Cancer Immunotherapeutic in Patients With Metastatic Melanoma

The purpose of this clinical study is to examine the safety, immunogenicity and clinical activity of the immunotherapeutic product GSK2302025A (also referred to as recPRAME + AS15 Antigen-Specific Cancer Immunotherapeutic [ASCI]) administered as a first line treatment in patients with unresectable and progressive metastatic cutaneous melanoma.

In this study, patients were to receive a maximum of 24 doses of recMAGE-A3 + AS15 according to four cycles over a period of four years. An active follow-phase (up to five years after registration into the study) was planned for all patients.

This protocol summary has been impacted by protocol amendment 3, so there will no longer be an active follow-up of patients after discontinuation or completion of the study treatment. The study will end approximately 30 days after the last dose will be administered.

In addition, no more biological samples will be collected for protocol research purposes. For each biological sample already collected in the scope of this study and not tested yet, testing will not be performed by default, except if a scientific rationale remains relevant.

Sampling for safety monitoring as per protocol will continue.

Inclusion Criteria:

1. Male or female patient with histologically proven cutaneous melanoma. Phase I segment: All melanoma patients with stage IV M1b and stage IV M1c including completely resected stage IV patients but with the exception of stage IV M1c disease with serum lactate dehydrogenase > 1.5 x Upper Limit of Normal or with involvement of the Central Nervous System.

   Phase II segment: All melanoma patients with measurable, unresectable stage III melanoma including in-transit metastasis (with (N3) or without (N2c) nodal metastasis) and stage IV M1a melanoma. The patient should have documented progressive disease within 12 weeks of registration into the trial. Patients with resected stage IV and with stage IV M1b or M1c disease cannot be included.

2. Written informed consent for PRAME expression screening and gene profiling on resected tumor tissue and for the complete study has been obtained from the patient prior to shipment of the sample for expression testing and prior to the performance of any other protocol-specific procedure.

3. The patient is >= 18 years old at the time of signing the first informed consent form.

4. The patient's tumor shows expression of the PRAME antigen as determined by RT-PCR analysis or any updated technique on fresh tissue sample.

5. Eastern Cooperative Oncology Group performance status of 0 or 1.

6. The patient has adequate bone marrow reserve, renal, adrenal and hepatic function as assessed by standard laboratory criteria.

7. Female patients of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as current tubal ligation, hysterectomy, ovariectomy or post-menopause.

8. Female patients of childbearing potential may be enrolled in the study, if the patient:

   • has practiced adequate contraception for 30 days prior to the study product administration, and
   • has a negative pregnancy test on the day of administration, and
   • has agreed to continue adequate contraception during the entire treatment period and for 2 months after the completion of the study product administration series.

9. In the view of the investigator, the patient can and will comply with all the requirements of the protocol.

Exclusion Criteria:

1. The patient has at any time received systemic chemotherapy, (bio)-chemotherapy or CTLA-4 monoclonal antibodies for metastatic disease.
2. The patient is scheduled to receive any other anticancer treatment, including but not limited to (bio)-chemotherapeutic or immunomodulating agents and radiotherapy.
3. The patient has received any cancer immunotherapy containing the PRAME antigen or any cancer immunotherapy for his/her metastatic disease.
4. The patient requires concomitant treatment (more than 7 consecutive days) with systemic corticosteroids or any other immunosuppressive agents.
5. Use of any investigational or non-registered product (drug or vaccine) other than the study product within the 30 days preceding the first ASCI dose injection or planned use during the study period
6. The patient has (had) previous or concomitant malignancies at other sites (including carcinoma in situ), except effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.
7. The patient has an allergy to any component of the study investigational product or has a history of previous allergic reactions to vaccinations.
8. The patient has a history of confirmed adrenal dysfunction.
9. The patient has an autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease.
10. The patient is known to be positive for the human immunodeficiency virus (HIV).
11. The patient has an uncontrolled bleeding disorder.
12. The patient has a family history of congenital or hereditary immunodeficiency.
13. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
14. The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
15. For female patients: the patient is pregnant or lactating.