NY-ESO-1 Vaccine in Combination With Ipilimumab in Patients With Unresectable or Metastatic Melanoma
Condition: Unresectable or Metastatic Melanoma
MeSH terms: Melanoma
Intervention: Ipilimumab; NY-ESO-1 Protein Vaccine; NY-ESO-1 OLP4 Vaccine with Poly-ICLC and Montanide; NY-ESO-1 OLP4 Vaccine with Poly-ICLC
Intervention description: Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses.; NY-ESO-1 recombinant protein (250 µg) was mixed with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.; NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.; NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.
Intervention MeSH terms: Poly I-C; Ipilimumab; Carboxymethylcellulose Sodium; Vaccines; Monatide (IMS 3015); Poly ICLC
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NY-ESO-1; Metastatic Melanoma; Ipilimumab; Phase I; Adjuvant; Immunologic; Vaccination; Immunotherapy; Neoplasm

Summary:

      This was a Phase 1, open-label, non-randomized study of the combination of NY-ESO-1 plus
      ipilimumab in patients with unresectable or metastatic melanoma for whom treatment with
      ipilimumab was indicated. Patients must have had evidence of NY-ESO-1 or LAGE-1 tumor
      positivity and radiologically measurable disease by the immune-related Response Criteria
      (irRC). Primary study objectives were to determine the safety and tolerability of the
      combination and to evaluate humoral and cellular immune response. Secondary objectives were
      to evaluate tumor response and immunological changes in the tumor microenvironment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with unresectable or metastatic melanoma, for whom treatment with ipilimumab
             was indicated as per ipilimumab/Yervoy® package insert (applicable for United States
             [US] sites) or product information (applicable for Australia site).

          2. Radiologically measurable disease by irRC.

          3. Tumor expression of NY-ESO-1 or LAGE-1 antigen by immunohistochemistry or reverse
             transcriptase-polymerase chain reaction (RT-PCR), or evidence of seropositivity to
             NY-ESO-1 or LAGE-1.

          4. Willingness to provide at least one pre-and post-vaccination tumor biopsy sample.

          5. Expected survival of at least 4 months.

          6. At the time of Day 1 of the study, patients must have been at least 3 weeks since
             surgery.

          7. At the time of Day 1 of the study, patients with brain metastases must have been
             asymptomatic and:

               -  at least 8 weeks without tumor progression after any whole brain radiotherapy;

               -  at least 4 weeks since craniotomy and resection or stereotactic radiosurgery;

               -  at least 3 weeks without new brain metastases as evidenced by magnetic resonance
                  imaging (MRI).

          8. Eastern Cooperative Oncology Group performance status of 0 to 2.

          9. Laboratory parameters for vital functions must have been in the normal range.
             Laboratory abnormalities that were not clinically significant were generally
             permitted, except for the following laboratory parameters, which must have been within
             the ranges specified:

               -  hemoglobin: ≥ 10 g/dL;

               -  neutrophil count: ≥ 1.5 x 10^9/L;

               -  lymphocyte count: ≥ lower limit of normal (LLN);

               -  platelet count: ≥ 80 x 10^9/L;

               -  serum creatinine: ≤ 2 mg/dL;

               -  serum bilirubin: ≤ 2 x upper limit of normal (ULN);

               -  aspartate aminotransferase (AST)/alanine aminotransferase (ALT): ≤ 2 x ULN.

         10. Had been informed of other treatment options.

         11. Age ≥ 18 years.

         12. Able and willing to give valid written informed consent.

        Exclusion Criteria:

          1. Any contraindications for ipilimumab/Yervoy® as per package insert (applicable for US
             sites) or product information (applicable for Australia site).

          2. Prior exposure to NY-ESO-1 vaccine.

          3. Active autoimmune disease, symptoms or conditions except for vitiligo, type I
             diabetes, treated thyroiditis, asymptomatic laboratory evidence of autoimmune disease
             (e.g., +antinuclear antibody [ANA], +rheumatoid factor [RF], antithyroglobulin
             antibodies), or mild arthritis requiring no therapy or manageable with nonsteroidal
             anti-inflammatory drugs (NSAIDs).

          4. Unresolved immune-related adverse events following prior biological therapy.

          5. Systemic treatment with high-dose corticosteroids (greater than prednisone 10 mg daily
             or equivalent).

          6. Treatment with protocol-specified non-permitted concomitant therapies.

          7. Metastatic disease to the central nervous system for which other therapeutic options,
             including radiotherapy, may have been available.

          8. 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.

          9. Other malignancy within 3 years prior to entry into the study, except for treated
             non-melanoma skin cancer and cervical carcinoma in situ.

         10. Known immunodeficiency or human immunodeficiency virus positivity, active Hepatitis B
             or active Hepatitis C.

         11. History of severe allergic reactions to vaccines or unknown allergens.

         12. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding
             disorders).

         13. Participation in any other clinical trial involving another investigational agent
             within 4 weeks prior to Day 1 of the study.

         14. Mental impairment that may have compromised the ability to give informed consent and
             comply with the requirements of the study.

         15. Lack of availability for immunological and clinical follow-up assessments.

         16. Women who were breast feeding or pregnant as evidenced by positive serum pregnancy
             test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin
             [HCG]) done within 14 days prior to first dosing and urine test within 72 hours prior
             to first dosing.

         17. Women of childbearing potential not using a medically acceptable means of
             contraception for the duration of the study.

         18. Any condition that, in the clinical judgment of the treating physician, was likely to
             prevent the patient from complying with any aspect of the protocol or that may have
             put the patient at unacceptable risk.