A Phase II Study of Nivolumab plus Ipilimumab versus Ipilimumab Alone in Patients with Previously Untreated Inoperable or Metastatic Melanoma

Full Title
Phase 2, Randomized, Double Blinded, Study of Nivolumab (BMS-936558) in Combination with Ipilimumab vs Ipilimumab Alone in Subjects with Previously Untreated, Unresectable or Metastatic Melanoma

The purpose of this study is to compare the effectiveness of the drugs nivolumab and ipilimumab given together compared with ipilimumab alone in patients with previously untreated inoperable or metastatic melanoma. Ipilimumab is already approved for treating melanoma. Nivolumab (also called BMS-936558) is investigational. Prior research has shown that the combination of these two drugs can be very effective for shrinking melanoma tumors.

Nivolumab boosts the body’s immune system by targeting a protein on white blood cells called PD-1. PD-1 normally maintains the balance of the immune system by shutting it down at the right time. Some cancers take advantage of this shut-down mechanism by activating PD-1, enabling them to escape attack by the body’s white blood cells. Nivolumab binds to and inactivates PD-1, enhancing the body’s ability to detect and destroy cancer cells.

Ipilimumab is an antibody against CTLA-4, a molecule that controls a part of the immune system by shutting it down. Researchers believe that an antibody against CTLA-4 could stop it from turning off the immune system, and allow an immune response that may help the body to destroy cancer cells.

Patients will be randomly assigned to receive nivolumab plus ipilimumab or ipilimumab plus a placebo. Nivolumab will be offered to patients in this study who initially do not benefit from ipilimumab alone. All treatments are given intravenously (by vein).


To be eligible for this study, patients must meet several criteria, including but not limited to the following:

  • Patients must have inoperable or metastatic (stage III or IV) melanoma and may not have previously received treatment for advanced disease.
  • For patients who previously received treatment for melanoma before or after surgery, at least 6 weeks must have passed since completion of prior therapy and the first dose of the study drugs (2 weeks since completing any radiation therapy).
  • A sufficient piece of melanoma tissue (such as a lymph node or other biopsy of distant disease) will need to be tested before receiving treatment. If such a sample is unavailable, a repeat biopsy will be required.
  • This study is open to patients with normal as well as mutated BRAF genes; all patients should have or will have their BRAF status tested so researchers can see how the different therapies work according to BRAF status.
  • Patients may not have previously received nivolumab, ipilimumab, or other drugs that target PD-1 or CTLA-4.
  • Patients must be physically well enough that they are fully ambulatory, capable of all self care, and are capable of all but physically strenuous activities. As an example, patients must be well enough that they would be able to carry out office work or light housework.
  • This study is open to patients ages 18 and older.

For more information and to inquire about eligibility for this study, please contact Dr. Michael Postow at 646-888-4589.

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