Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Multicenter Study Comparing MDX-010 Monotherapy, MDX-010 in Combination With a Melanoma Peptide Vaccine, and Melanoma Vaccine Monotherapy in HLA-A2*0201-Positive Patients With Previously Treated Unresectable Stage III or IV Melanoma
Brief 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.


Options:
A: Inclusion Criteria:

* The lesion is pigmented (i.e., melanin, keratin, blood)
* Clinical management of the lesion by the examining dermatologist is either biopsy of the lesion in toto, or 3-month follow-up of the lesion
* The diameter of the pigmented area is between 2 and 22 millimeters
* The lesion is accessible to the MelaFind hand-held imaging device
* The patient, or a legally authorized representative, has consented to participate in the study and has signed the Informed Consent Form

Exclusion Criteria:

* The patient has a known allergy to isopropyl alcohol
* The lesion has been previously biopsied, excised, or traumatized
* The skin is not intact (e.g., open sores, ulcers, bleeding)
* The lesion is within 1 cm of the eye
* The lesion is on mucosal surfaces (e.g., lips, genitals)
* The lesion is on palmar hands
* The lesion is on plantar feet
* The lesion is on or under nails
* The lesion is located on or in an area of visible scarring
* The lesion contains foreign matter (e.g., tattoo, splinter, marker)
B: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Key Inclusion Criteria:

* Eastern Cooperative Oncology Group performance status of 0 or 1
* Histologically confirmed unresectable Stage III or Stage IV melanoma
* No prior systemic anticancer therapy for unresectable or metastatic melanoma. Note that prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to date of first dose, and all related adverse events have either returned to baseline or stabilized
* Tumor tissue obtained in the metastatic setting or from an unresectable site must be provided for biomarker analyses and sent to the central laboratory. Biopsy should be excisional, incisional punch, or core needle. Fine needle aspirates or other cytology samples are insufficient
* Known BRAF V600 mutation status as determined by an FDA-approved test. Patients with either V600 wild-type or V600 mutation-positive melanoma are eligible.

Key Exclusion Criteria:

* Active brain metastases or leptomeningeal metastases. Patients with treated brain metastases are eligible if there is no evidence of progression on magnetic resonance imaging scan for at least 8 weeks after completion of treatment and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (\>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
* Ocular melanoma
* Patients with active, known, or suspected autoimmune disease. Those with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
C: Inclusion Criteria:

* Participants with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th edition. Unresectability of stage IIIc disease must have confirmation from a surgical oncologist
* Participants must be naïve to treatment for locally advanced unresectable or metastatic disease (ie, no prior systemic anti-cancer therapy for advanced disease; stage IIIc and IV). Prior adjuvant immunotherapy (including ipilimumab) is allowed
* Documentation of BRAF V600 mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples) using the cobas 4800 BRAF V600 mutation test
* Measurable disease per RECIST v1.1
* Eastern Clinical Oncology Group performance status of 0 or 1
* Consent to provide archival for biomarker analyses
* Consent to undergo tumor biopsies for biomarker analyses
* Life expectancy greater than or equal to (≥) 12 weeks
* Adequate hematologic and end organ function

Exclusion Criteria:

* History of prior rapidly accelerated fibrosarcoma or mitogen-activated protein kinase pathway inhibitor treatment
* Palliative radiotherapy within 14 days prior to the first dose of study treatment
* Major surgery or traumatic injury within 14 days prior to first dose of study treatment
* Active malignancy other than melanoma that could potentially interfere with the interpretation of efficacy measures. Participants with a previous malignancy within the past 3 years are excluded except for participants with resected basal cell carcinoma or squamous cell carcinoma of the skin, melanoma in-situ, carcinoma in-situ of the cervix, and carcinoma in-situ of the breast
* History of or evidence of retinal pathology on ophthalmological examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion, or neovascular macular degeneration
* Uncontrolled glaucoma with intraocular pressure
* Serum cholesterol ≥ Grade 2
* Hypertriglyceridemia ≥ Grade 2
* Hyperglycemia (fasting) ≥ Grade 2
* History of clinically significant cardiac dysfunction
* Participants with active central nervous system (CNS) lesions (including carcinomatous meningitis) are excluded. However, participants are eligible if:

  1. All known CNS lesions have been treated with stereotactic therapy or surgery, AND
  2. There has been no evidence of clinical and radiographic disease progression in the CNS for ≥ 3 weeks after radiotherapy or surgery
* Current severe, uncontrolled systemic disease
* History of malabsorption or other condition that would interfere with absorption of study drugs
* Pregnant, lactating, or breast feeding women
D: 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

Answer: D