Evaluation of a New Anti-cancer Immunotherapy in Patients With Non-operable and Progressing Metastatic Cutaneous Melanoma

• Occurrence of severe toxicities. [ Time Frame: On continuous basis during the study treatment period (49 months) and active follow-up period (one year). ] [ Designated as safety issue: No ]
• The induction of objective clinical response (Complete Response (CR) or Partial Response (PR)) in the overall population. Week 12 [ Time Frame: After 12 weeks of treatment. ] [ Designated as safety issue: No ]
• The induction of objective clinical response (Complete Response (CR) or Partial Response (PR)) in the overall population. Week 22 [ Time Frame: After 22 weeks of treatment. ] [ Designated as safety issue: No ]
• The induction of objective clinical response (Complete Response (CR) or Partial Response (PR)) in the overall population. Week 31 [ Time Frame: After 31 weeks of treatment. ] [ Designated as safety issue: No ]
• The induction of objective clinical response (Complete Response (CR) or Partial Response (PR)) in the overall population. Week 54 [ Time Frame: After 54 weeks of treatment. ] [ Designated as safety issue: No ]
• The induction of objective clinical response (Complete Response (CR) or Partial Response (PR)) in the overall population. 1 Year 6 Months [ Time Frame: After 1 year and six months of treatment. ] [ Designated as safety issue: No ]
• The induction of objective clinical response (Complete Response (CR) or Partial Response (PR)) in the overall population. 2 Years [ Time Frame: After 2 years of treatment. ] [ Designated as safety issue: No ]
• The induction of objective clinical response (Complete Response (CR) or Partial Response (PR)) in the overall population. 2 Years 6 Months [ Time Frame: After 2 years and six months of treatment. ] [ Designated as safety issue: No ]
• The induction of objective clinical response (Complete Response (CR) or Partial Response (PR)) in the overall population. 3 Years [ Time Frame: After 3 years of treatment. ] [ Designated as safety issue: No ]
• The induction of objective clinical response (Complete Response (CR) or Partial Response (PR)) in the overall population. 3 Years 6 Months [ Time Frame: After 3 years and six months of treatment. ] [ Designated as safety issue: No ]
• The induction of objective clinical response (Complete Response (CR) or Partial Response (PR)) in the overall population. 4 Years 1 Month [ Time Frame: After 4 years and 1 month of treatment. ] [ Designated as safety issue: No ]
• The induction of objective clinical response (Complete Response (CR) or Partial Response (PR)) in the overall population. 4 Years 7 Months [ Time Frame: After 4 years and 7 months of treatment. ] [ Designated as safety issue: No ]
• The induction of objective clinical response (Complete Response (CR) or Partial Response (PR)) in the overall population. 5 Years 1 Month [ Time Frame: After 5 years and 1 months of treatment. ] [ Designated as safety issue: No ]

• Occurrence of objective clinical response (CR or PR) in the population of patients who present the predictive Melanoma Antigen A3 (MAGE-A3) gene signature. [ Time Frame: After 12, 22, 31 and 54 weeks of treatment and subsequently after 1 year and six months, 2 years, 2 years and six months, 3 years, 3 years and six months, 4 years and one month, 4 years and 7 months, and 5 years and 1 month. ] [ Designated as safety issue: No ]
• Occurrence of adverse events (AEs) and serious adverse events (SAEs). [ Time Frame: On continuous basis during the study treatment period and ending 30 days after the last study treatment administration (49 months). ] [ Designated as safety issue: No ]
• Immunogenicity of the NY-ESO-1 ASCI treatment. [ Time Frame: At start of treatment, after 4, 8, 10, 12, 30 and 52 weeks of treatment and after 1 year and six months, 2 yrs, 2 yrs and six months, 3 yrs, 3 yrs and six months, 4 yrs and one month, 4 yrs and four months, 4 yrs and 7 months, and 5 yrs and 1 month. ] [ Designated as safety issue: No ]
• In the overall population and in the population of patients presenting the predictive MAGE-A3 gene signature: Occurrence of stable disease (SD). [ Time Frame: Throughout the study treatment period (49 months) and follow-up period. ] [ Designated as safety issue: No ]
• In the overall population and in the population of patients presenting the predictive MAGE-A3 gene signature: Occurrence of mixed response (MR). [ Time Frame: Throughout the study treatment period (49 months) and follow-up period. ] [ Designated as safety issue: No ]
• In the overall population and in the population of patients presenting the predictive MAGE-A3 gene signature: Time to Treatment Failure (TTF). [ Time Frame: Throughout the study treatment period (49 months) and follow-up period. ] [ Designated as safety issue: No ]
• In the overall population and in the population of patients presenting the predictive MAGE-A3 gene signature: Progression-free survival (PFS). [ Time Frame: Throughout the study treatment period (49 months) and follow-up period. ] [ Designated as safety issue: No ]
• In the overall population and in the population of patients presenting the predictive MAGE-A3 gene signature: Overall survival (OS). [ Time Frame: Throughout the study treatment period (49 months) and follow-up period. ] [ Designated as safety issue: No ]
• In the overall population and in the population of patients presenting the predictive MAGE-A3 gene signature: The duration of response for patients with CR, PR or Stable Disease (SD) status. [ Time Frame: Throughout the study treatment period (49 months) and follow-up period. ] [ Designated as safety issue: No ]

• Occurrence of objective clinical response (CR or PR) in the population of patients who present the predictive Melanoma Antigen A3 (MAGE-A3) gene signature. [ Time Frame: After 12, 23, 32 and 54 weeks of treatment and subsequently after 1 year and six months, 2 years, 2 years and six months, 3 years, 3 years and six months, 4 years and one month, 4 years and 7 months, and 5 years and 1 month ] [ Designated as safety issue: No ]
• Occurrence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: On continuous basis during the study treatment period and ending 30 days after the last study treatment administration (49 months). ] [ Designated as safety issue: No ]
• Immunogenicity to immunotherapy constituents [ Time Frame: at start of treatment, after 4, 8, 10 12, 30 and 52 weeks of treatment and subsequently after 1,5 years, 2 years, 2,5 years, 3 years, 3,5 years, 4 years and 1 month, 4 years and 4 months, 4 years and 7 months, and 5 years and 1 month. ] [ Designated as safety issue: No ]
• In the overall population and in the population of patients presenting the predictive MAGE-A3 gene signature: Occurrence of stable disease (SD). [ Time Frame: Throughout the study treatment period (49 months) and follow-up period. ] [ Designated as safety issue: No ]
• In the overall population and in the population of patients presenting the predictive MAGE-A3 gene signature: Occurrence of mixed response (MR). [ Time Frame: Throughout the study treatment period (49 months) and follow-up period. ] [ Designated as safety issue: No ]
• In the overall population and in the population of patients presenting the predictive MAGE-A3 gene signature: Time to Treatment Failure (TTF). [ Time Frame: Throughout the study treatment period (49 months) and follow-up period. ] [ Designated as safety issue: No ]
• In the overall population and in the population of patients presenting the predictive MAGE-A3 gene signature: Progression-free survival (PFS). [ Time Frame: Throughout the study treatment period (49 months) and follow-up period. ] [ Designated as safety issue: No ]
• In the overall population and in the population of patients presenting the predictive MAGE-A3 gene signature: Overall survival (OS). [ Time Frame: Throughout the study treatment period (49 months) and follow-up period. ] [ Designated as safety issue: No ]
• In the overall population and in the population of patients presenting the predictive MAGE-A3 gene signature: The duration of response for patients with CR, PR or Stable Disease (SD) status. [ Time Frame: Throughout the study treatment period (49 months) and follow-up period. ] [ Designated as safety issue: No ]

This study is investigating the safety, immunogenicity and clinical activity of GSK2241658A antigen-specific cancer immunotherapeutic (ASCI) for the treatment of patients with non-operable and progressing metastatic cutaneous melanoma.

Inclusion Criteria:

• Male or female patient with histologically proven, measurable metastatic cutaneous melanoma, and with documented progressive disease within the 12 weeks before the first administration of study treatment.
• Written informed consent for NY-ESO-1 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.
• Patient is >= 18 years of age at the time of signature of the informed consent.
• The patient's tumor shows expression of NY-ESO-1, as determined by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis or any updated technique on fresh tissue sample(s).
• Eastern Cooperative Oncology Group performance status of 0 or 1.

• The patient has normal organ functions as shown by all of the following:

  • Hemoglobin ≥ 12 g/dL
  • Absolute leukocytes count ≥ 3.0 x 1000000000/L
  • Absolute lymphocytes count ≥ 1.0 x 1000000000/L
  • Platelets ≥ 100 x 1000000000/L
  • Serum creatinine ≤ Upper Limit of Normal (ULN)
  • Serum total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's syndrome for whom the limit is 2 x ULN)
  • Lactate dehydrogenase ≤ ULN
  • Aspartate aminotransferase ≤ 2 × ULN
  • Alanine aminotransferase ≤ 2 × ULN

These tests must be done no more than 3 weeks before the first ASCI administration.

• Female patients of non-childbearing potential may be enrolled in the study.

• Female patient of childbearing potential may be enrolled in the study, if the patient:

  • has practiced adequate contraception for 30 days prior to first ASCI administration, and
  • has a negative pregnancy test at the specified study visits, and
  • has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the ASCI administration series.
• In the view of the investigator, the patient can and will comply with the requirements of this protocol.

Exclusion Criteria:

• The patient has at any time received systemic chemotherapy, biochemotherapy, small molecules or nti-CTLA-4 monoclonal antibody for metastatic disease.
• The patient is scheduled to receive any other anticancer treatments than those specified in the protocol, including but not limited to (bio-) chemotherapeutic, immunomodulating agents and radiotherapy.
• The patient received any cancer immunotherapy containing a NY-ESO-1 antigen or any cancer immunotherapy for his/her metastatic disease.
• The patient requires concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents.
• Use of any investigational or non-registered product other than the ASCI within 30 days preceding the first ASCI administration, or planned use during the study period.
• The patient has (had) previous or concomitant malignancies at other sites, 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.
• The patient has an allergy to any component of the study investigational product or has a history of previous allergic reactions to vaccinations.
• The patient has an autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.
• The patient has a family history of congenital or hereditary immunodeficiency.
• The patient is known to be positive for the Human Immunodeficiency Virus.
• The patient has an uncontrolled bleeding disorder.
• The patient has a family history of congenital or hereditary immunodeficiency.
• The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the trial procedures.
• The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
• For female patients: the patient is pregnant or lactating.