Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: NY-ESO-1 Vaccine in Combination With Ipilimumab in Patients With Unresectable or Metastatic Melanoma

Summary: The purpose of this study is to evaluate the safety, tolerability and immunogenicity of Ipilimumab i.v. followed by NY-ESO-1 Protein vaccine with Poly-ICLC and Montanide s.c. (Arm A), or NY-ESO-1 OLP4 vaccine with Poly-ICLC and Montanide s.c. (Arm B), or NY-ESO-1 OLP4 vaccine mixed with Poly-ICLC without Montanide s.c.(Arm C).

Detailed description: This is a phase I, open-label, non-randomized study in 27 patients with unresectable or metastatic melanoma, for whom treatment with ipilimumab is indicated. Patients must have evidence of NY-ESO-1 or LAGE-1 tumor positivity, radiologically measurable disease by immune-related Response Criteria (irRC), and meet all other eligibility criteria.

Eligibility: Inclusion Criteria:
  -  Patients with unresectable or metastatic melanoma, for whom treatment with ipilimumab is indicated as per ipilimumab/Yervoy® package insert (applicable for US sites) or product information (applicable for Australia site).
  -  Radiologically measurable disease by immune-related Response Criteria (irRC).
  -  Tumor expression of NY-ESO-1 or LAGE-1 antigen by IHC or RT-PCR, or evidence of seropositivity to NY-ESO-1 or LAGE-1.
  -  Willingness to provide at least one pre-and post-vaccination tumor biopsy sample.
  -  Expected survival of at least 4 months.
  -  At the time of day 1 of the study, patients must be at least 3 weeks since surgery.
  -  At the time of day 1 of the study, patients with brain metastases must be asymptomatic and: 1) at least 8 weeks without tumor progression after any whole brain radiotherapy, 2) at least 4 weeks since craniotomy and resection or stereotactic radiosurgery, 3) at least 3 weeks without new brain metastases as evidenced by MRI
  -  ECOG performance status of 0-2.
  -  The following laboratory parameters must be within the ranges specified: Hemoglobin ≥ 10 g/dL, Neutrophil count ≥ 1.5 x 109/L, Lymphocyte count ≥ LLN Platelet count ≥ 80 x 109/L, Serum creatinine ≤ 2 mg/dL, Serum bilirubin ≤ 2 x ULN, AST/ALT ≤ 2 x ULN.
  -  Have been informed of other treatment options.
  -  Age ≥ 18 years.
  -  Able and willing to give valid written informed consent.
  Exclusion Criteria:
  -  Any contraindications for ipilimumab/Yervoy® as per package insert(applicable for US sites) or product information (applicable for Australia site).
  -  Prior exposure to NY-ESO-1 vaccine.
  -  Active autoimmune disease, symptoms or conditions except for vitiligo, type I diabetes, treated thyroiditis, asymptomatic laboratory evidence of autoimmune disease (e.g.: +ANA, +RF, antithyroglobulin antibodies), or mild arthritis requiring no therapy or manageable with NSAIDs.
  -  Unresolved immune related adverse events following prior biological therapy.
  -  Systemic treatment with high dose corticosteroids (greater than Prednisone 10mg daily or equivalent).
  -  Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available.
  -  Myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, chest pain or shortness of breath with activity, or other heart conditions being treated by a doctor.
  -  Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
  -  Known immunodeficiency or HIV positivity, active Hepatitis B or active Hepatitis C.
  -  History of severe allergic reactions to vaccines or unknown allergens.
  -  Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
  -  Participation in any other clinical trial involving another investigational agent within 4 weeks prior to day 1 of the study.
  -  Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
  -  Lack of availability for immunological and clinical follow-up assessments.
  -  Women who are breast feeding or pregnant as evidenced by pregnancy test.
  -  Women of childbearing potential not using a medically acceptable means of contraception for the duration of the study.
  -  Any condition that, in the clinical judgment of the treating physician, is likely to prevent the patient from complying with any aspect of the protocol or that may put the patient at unacceptable risk.

Relevance to patient case: not relevant