Monoclonal Antibody With or Without gp100 Peptides Plus Montanide ISA-51 in Treating Patients With Stage IV Melanoma

OBJECTIVES:

Primary

• Determine the clinical response in patients with stage IV melanoma treated with escalating doses of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) with or without gp100 peptides emulsified in Montanide ISA-51.

Secondary

• Determine the safety and toxicity profile of these regimens in these patients.
• Determine the immunologic response in patients treated with these regimens.
• Determine the pharmacokinetics of these regimens in these patients.
• Determine, in HLA-A*0201-positive patients, the differences in responses between patients previously vaccinated with gp100 peptides and patients not previously vaccinated.

OUTLINE: This is a 2-part, partially randomized study.

• Part I (closed as of 3/7/2005):

  • HLA-A*0201-negative patients: Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 3 weeks for up to 6 doses (3 courses of 3 escalating doses) in the absence of disease progression or unacceptable toxicity.

  • HLA-A*0201-positive patients: Patients are stratified according to prior exogenous gp100 peptide immunization (yes vs no). Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive MDX-010 in the same manner as the HLA-A*0201-negative patients.
    • Arm II: Patients receive MDX-010 as in arm I. Patients also receive gp100:209-217 and gp100:280-288 peptides emulsified in Montanide ISA-51 subcutaneously immediately after each MDX-010 infusion.

• Part II:

  • HLA-A*0201-negative patients (closed as of 3/7/2005): Patients receive MDX-010 as in part I. Treatment repeats every 3 weeks for up to 4 doses (2 courses of 2 escalating doses, beginning with a higher dose level than in part I) in the absence of disease progression or unacceptable toxicity.

  • HLA-A*0201-positive patients: Patients are stratified and randomized as in part I.

    • Arm I: Patients receive MDX-010 in the same manner as the HLA-A*0201-negative patients.
    • Arm II: Patients receive MDX-010 as in arm I. Patients also receive gp100:209-217 and gp100:280-288 peptides emulsified in Montanide ISA-51 subcutaneously immediately after each MDX-010 infusion.

In both parts, patients with stable disease or a complete response (CR) after completing all courses of MDX-010 may receive 1 additional course of therapy in the absence of unacceptable toxicity. Patients achieving a partial response may continue to recieve treatment with MDX-010 at the same dose, in the absence of unacceptable toxicity, until CR or until tumor is no longer shrinking.

Patients are followed at 3 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 35-179 patients (up to 35 for part I [closed as of 3/7/05] and 69-141 [23-47 per arm (arm I closed as of 3/7/05)] for part II) will be accrued for this study within 3-4 years.