Nivolumab (Opdivo®) + Ipilimumab (Yervoy®)

Immunotherapy for advanced melanoma activates your immune system to attack the cancer cells. Cancer researchers are developing more effective ways to treat advanced melanoma, including using some drugs in combination.

When used together, nivolumab and ipilimumab can treat advanced melanoma more effectively than each drug on its own. This combination of two immunotherapy drugs can shrink tumors and help patients live longer.

What Are Nivolumab (Opdivo) + Ipilimumab (Yervoy)?

Nivolumab is an anti-PD-1 drug, which is an antibody that promotes the tumor-killing effects of T-cells (white blood cells that help your body fight disease). Ipilimumab is an anti-CTLA-4 drug, which is an antibody that helps strengthen the immune system by promoting the function and growth of T-cells.

Both medications:

  • Are a type of immunotherapy known as checkpoint inhibitors, a type of immunotherapy that energizes your body's own immune system to attack the cancer cells
  • Help slow or stop the growth and spread of melanoma cells

Learn more about nivolumab (Opdivo) and ipilimumab (Yervoy) as separate drugs.

Watch our video about how checkpoint inhibitor immunotherapy offers new hope to patients who have advanced melanoma:

How Do Nivolumab and Ipilimumab Work Together?

Your immune system uses certain molecules on immune cells that act as checkpoints to prevent attacks on healthy cells and minimize autoimmune disease. Melanoma cells can sometimes take advantage of these checkpoint molecules to avoid being detected by the immune system.

Nivolumab and ipilimumab target and block two different checkpoints, which increases your body's immune response. In this way, the drugs activate immune cells—unleashing them, in effect—so that they can invade tumors and attack melanoma cells.

Ipilimumab blocks a checkpoint molecule called CTLA-4. CTLA-4 regulates the growth and activity of T cells, a type of white blood cell that attacks other cells in the body that look foreign, including some cancer cells. By blocking CTLA-4, ipilimumab activates your immune system against melanoma by allowing T cells to multiply and increase your body's immune response.

Nivolumab blocks a different checkpoint molecule called PD-1, which helps protect tumor cells from being attacked by your immune system. Nivolumab removes the PD-1 "shield" to allow your immune system to find and attack melanoma cells.

Ipilimumab essentially turns on the immune response, allowing T cells to begin the attack on melanoma. Nivolumab then removes the immune protection that cancer cells put up to defend themselves from attacks.

Nivolumab and ipilimumab are systemic, which means that the treatments travel through the bloodstream to reach all parts of the body. Cancer physicians use systemic immunotherapy to treat metastatic cancer, which is cancer that has spread from its original location to other areas of the body.

Watch Dr. Evan J. Lipson of Johns Hopkins Medicine discuss combination therapy for advanced melanoma.

Which Patients May Benefit from Nivolumab and Ipilimumab?

The U.S. Food and Drug Administration (FDA) approved the use of nivolumab in combination with ipilimumab to treat patients who have advanced stages of melanoma:

  • Stage III that is unresectable (unable to be completely removed by surgery)
  • Stage IV, also known as metastatic (melanoma cells that have spread to organs and other parts of the body)

How Are Nivolumab and Ipilimumab Given?

Patients receive both medications intravenously (into a blood vein). During the first phase of this therapy, patients receive both medications on the same day, as follows:

  • The recommended dose and schedule of nivolumab is 1 mg/kg administered intravenously over 60 minutes.
  • For ipilimumab, the recommended dose is 3 mg/kg administered intravenously over 90 minutes.
  • This combination regimen continues every 3 weeks for a total of 4 doses.

After 4 doses, patients move on to the second phase of treatment and receive only nivolumab. The recommended dose of nivolumab as a single agent is 3 mg/kg administered intravenously over 60 minutes every 2 weeks.

Patients usually continue to take these medications for a period of time, until their melanoma worsens or they experience unacceptable side effects. Depending on how you respond to treatment, your physician may adjust your doses. 

What Are the Goals of Nivolumab and Ipilimumab?

The combination of nivolumab and ipilimumab works as a systemic treatment to promote an immune response, with the goals of:

  • Controlling melanoma and shrinking tumors anywhere in the body
  • Treating symptoms of melanoma
  • Helping patients live longer

This combination therapy of antibodies helps build up your immune system, which has an immunological "memory." That means that nivolumab and ipilimumab may help your immune system continue to attack melanoma cells even after treatment. 

In a phase II clinical trial in 2015, the nivolumab and ipilimumab combination therapy showed a higher response rate compared with ipilimumab alone. The results mean that more patients taking the combination therapy experienced melanoma tumor shrinkage if they received nivolumab and ipilimumab versus ipilimumab by itself. 

Melanoma treatments, like nivolumab and ipilimumab, have side effects, which can be more serious when the drugs are combined. Patients should talk with their physician to learn more about the side effects of this combination therapy and other melanoma treatment options.

What Should I Ask My Doctor About Nivolumab and Ipilimumab?

Not all treatments work for all patients with melanoma, because everyone is different. If you are interested in learning more about the combination of nivolumab and ipilimumab, here are some questions you should ask your physicians:

  • Am I eligible for nivolumab and ipilimumab?
  • What is your experience with nivolumab and ipilimumab?
  • Is this combination therapy a good option for my melanoma treatment?
  • Is there an alternative to nivolumab and ipilimumab for me?
  • How successful has the combination been for patients like me?
  • What are the side effects of nivolumab and ipilimumab?
  • Are there any clinical trials for the combination therapy that I should consider?
  • What other treatments are FDA-approved for treating advanced melanoma?
  • What are the risks and benefits of the available treatment options?
  • What are the goals for my treatment?
  • How long will I stay on this treatment?

Need Help Paying for Nivolumab (Opdivo) + Ipilimumab (Yervoy)?

Patient Assistant Programs (PAPs) are designed so that you still have access to the treatments you need, in any financial circumstance. Learn more about the manufacturer’s patient assistance program and other options here.

Manufacturer’s Patient Assistance


Latest Treatments for Advanced Melanoma

Learn more about the latest, most effective treatments for patients who have advanced melanoma:

Melanoma Research

The Melanoma Research Alliance is the largest, non-profit funder of melanoma research worldwide. Since 2007, we have directly funded over $131 million in innovative grants to improve prevention, detection, and treatment of melanoma. We have also leveraged an additional $415 million in outside funds for research. Learn more about our funded research.

Last updated: August, 2021