Phase I Study of NY-ESO-1 Vaccine in Combination With Ipilimumab in Patients With Unresectable or Metastatic Melanoma, for Whom Treatment With Ipilimumab is Indicated.
- Patients with unresectable or metastatic melanoma, for whom treatment with ipilimumab
is indicated as per ipilimumab/Yervoy® package insert.
- 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.
- Any contraindications for ipilimumab/Yervoy® as per package insert.
- Prior exposure to NY-ESO 1 vaccine or anti CTLA-4 monoclonal antibodies.
- 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 (equivalent to or greater than
Prednisone 10mg daily).
- 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
- 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 positive serum pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of HCG) done within 72 hours of
- 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.