Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination Treatment for Patients With Unresectable or Metastatic Melanoma

Summary: The purpose of this study is to determine the safety and efficacy of MDX-010 (ipilimumab, BMS-734016) (anti-CTLA4) in combination with MDX-1379 (gp100, BMS-734019) in patients with previously treated, unresectable Stage III or IV melanoma. Survival time will be evaluated, as well as patient responses and time to disease progression. Eligible patients are those who in response to a single regimen containing interleukin-2 (IL-2), dacarbazine, and/or temozolomide, have 1) relapsed following an objective response (partial response/complete response [PR/CR]); 2) failed to demonstrate an objective response (PR/CR); or 3) could not tolerate such a regimen due to unacceptable toxicity. Patients will be randomized into one of three groups, and will receive one of the following treatments: MDX-010 alone, MDX-1379 alone, or MDX-010 in combination with MDX-1379.

Detailed description: Melanoma accounts for approximately 5% of all skin cancers in the United States, but it accounts for about 75% of all skin cancer deaths. In 2004, the expected prevalence of melanoma is 627,252, with about 119,178 of these cases being Stage III or IV (metastatic melanoma). First line treatments for metastatic melanoma, usually IL-2, dacarbazine and/or temozolomide, are associated with significant toxicities. MDX-010 (anti-CTLA4) antibodies are designed to keep the immune system running by blocking CTLA-4 from down-regulating T cell activation. MDX-1379 is made up of two peptides that are pieces of a bigger melanoma protein (gp100). These peptides bind to HLA-A2 which is then recognized by T cells.

Eligibility: Inclusion Criteria:
  -  Diagnosed with malignant melanoma
  -  Measurable unresectable Stage III or IV melanoma
  -  HLA-A*0201 positive
  -  Previous treatment with & failure/relapse/inability to tolerate IL-2, dacarbazine and/or temozolomide
  -  At least 4 weeks since prior treatment
  -  Negative pregnancy
  -  Life expectancy greater than 4 months
  -  Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1
  -  Required lab values
  -  Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) negative
  Exclusion Criteria:
  -  Prior malignancies which the patient has not been disease free for over 5 years, except treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer
  -  Ocular melanoma
  -  Active, untreated central nervous system (CNS) metastasis
  -  Prior treatment with MDX-010 (anti-CTLA4) antibody
  -  Prior treatment with any cancer therapeutic vaccine
  -  Active autoimmune disease or history of autoimmune disease
  -  Pregnancy or nursing
  -  Hypersensitivity to Incomplete Freund's Adjuvant (IFA) (Montanide ISA-51)
  -  Underlying medical conditions deemed hazardous if treated with study drug
  -  Concomitant therapy with anti-melanoma drugs, chemotherapies, other investigational therapies, chronic use of systemic corticosteroids
  -  Unable to provide informed consent

Relevance to patient case: not relevant