For people with advanced melanoma

OPDIVO® (nivolumab) is a prescription medicine used to treat people with a type of skin cancer called melanoma that has spread or cannot be removed by surgery (advanced melanoma).

OPDIVO is a prescription medicine used in combination with YERVOY® (ipilimumab) to treat people with a type of skin cancer called melanoma that has spread or cannot be removed by surgery (advanced melanoma).

It is not known if OPDIVO is safe and effective in children younger than 18 years of age.

For adults with advanced melanoma

OPDIVO and OPDIVO + YERVOY are not approved for patients
younger than 18 years of age.

OPDIVO and OPDIVO + YERVOY® (ipilimumab): Proven in a Clinical Trial for Advanced Melanoma

About the Clinical Trial


FDA-APPROVED FOR BOTH TYPES OF PATIENTS

OPDIVO® (nivolumab) + YERVOY® (ipilimumab) were studied in both BRAF- and BRAF+ patients

This study included both BRAF negative (normal BRAF gene or “wild” type) and BRAF positive (abnormal BRAF gene or “mutant” type) patients

BRAF is a gene involved in cell growth and other functions. An abnormal BRAF gene could cause cells to become cancerous.

While your doctor may test you for the BRAF biomarker to help you consider your treatment options, OPDIVO and OPDIVO + YERVOY are FDA-approved to treat advanced melanoma regardless of your test results.

The OPDIVO® (nivolumab) + YERVOY® (ipilimumab) clinical trial included 945 patients with previously untreated advanced melanoma.

OVER 50% of people alive
at 5 years


IN A FOLLOW-UP ANALYSIS FOR
THIS STUDY

2X as many patients were alive at
5 YEARS

52% of patients treated with OPDIVO® (nivolumab) + YERVOY® (ipilimumab) were alive at 5 years versus 26% treated with YERVOY® (ipilimumab) alone

The follow-up analysis at 5 years is consistent with the earlier (primary) analysis at 28 months. At 28 months, OPDIVO + YERVOY reduced the risk of dying by 45% compared to YERVOY alone. Half the patients on YERVOY were alive at 19.9 months, compared to more than half being alive with OPDIVO + YERVOY.

FDA-APPROVED FOR BOTH TYPES OF PATIENTS
A separate analysis looking at results by BRAF status

OPDIVO® (nivolumab) + YERVOY® (ipilimumab) demonstrated a 60% reduction in the risk of progression for BRAF+ patients and a 48% reduction in the risk of progression for BRAF- patients

In a follow-up analysis for this trial at 5 years,
People taking OPDIVO + YERVOY were living without cancer
spreading, growing, or getting worse more than 3x longer
than patients on YERVOY alone

Half of the patients on OPDIVO + YERVOY went 11.5 months without cancer spreading,
growing, or getting worse

versus

2.9 months with YERVOY alone

The follow-up analysis at 5 years is consistent with the earlier (primary) analysis at 9 months. At 9 months, OPDIVO + YERVOY reduced the risk of cancer spreading, growing, or getting worse by 58% compared to YERVOY alone.

IN A FOLLOW-UP ANALYSIS FOR THIS STUDY AT 5 YEARS,

OVER 3X as many people responded to
OPDIVO + YERVOY compared to YERVOY alone


OPDIVO +
YERVOY
(n=314)
YERVOY
alone
(n=315)

50%

tumors shrank or disappeared completely

15%


32%

tumors shrank
(partial response)

10%

18%

tumors disappeared completely
(complete response)

5%

At the earlier (primary) analysis at 9 months for OPDIVO + YERVOY, 50% of all tumors shrank or disappeared completely (41% of tumors shrank and 9% of tumors disappeared completely). For YERVOY alone, 14% of all tumors shrank or disappeared completely (12% of tumors shrank and 2% of tumors disappeared completely).


A SEPARATE ANALYSIS
LOOKED AT RESULTS BY
BRAF STATUS


OPDIVO +
YERVOY
(n=103)
YERVOY
alone
(n=100)

58%

tumors shrank or disappeared completely

15%


38%

tumors shrank
(partial response)

10%

20%

tumors disappeared completely
(complete response)

5%

OPDIVO +
YERVOY
(n=211)
YERVOY
alone
(n=215)

46%

tumors shrank or disappeared completely

14.4%


29%

tumors shrank
(partial response)

9.8%

17%

tumors disappeared completely
(complete response)

4.7%


When a tumor reacts to treatment, it shrinks. This is called a response

What does tumor response mean?

When a tumor reacts to treatment, it shrinks. This is called a response.

For OPDIVO alone clinical trial results, click here.

OPDIVO will not work for everyone. Individual results may vary.

SELECT IMPORTANT FACTS


What are the serious side effects of OPDIVO and OPDIVO + YERVOY?

OPDIVO can cause problems that can sometimes become serious or life-threatening and can lead to death. Serious side effects may include:

  • lung problems (pneumonitis)
  • intestinal problems (colitis) that can lead to tears or holes in
    your intestine
  • liver problems (hepatitis)
  • hormone gland problems (especially the thyroid, pituitary,
    adrenal glands, and pancreas)
  • kidney problems, including nephritis and kidney failure
  • skin problems
  • inflammation of the brain (encephalitis)
  • problems in other organs
  • severe infusion reactions

Additional serious side effects observed during a separate study of YERVOY alone include:

  • nerve problems that can lead to paralysis
  • eye problems

What are the most common side effects?

The most common side effects of OPDIVO when used in combination with YERVOY include:

  • feeling tired
  • rash
  • diarrhea
  • nausea
  • fever
  • pain in muscles, bones, and joints
  • upper respiratory tract infection
  • itching
  • abdominal pain
  • vomiting
  • cough
  • decreased appetite
  • shortness of breath

The most common side effects of YERVOY include:

  • feeling tired
  • diarrhea
  • nausea
  • itching
  • rash
  • vomiting
  • headache
  • weight loss
  • fever
  • decreased appetite
  • difficulty falling or staying asleep

These are not all of the possible side effects. Talk to your healthcare team for more information. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call

Important Facts About OPDIVO® (nivolumab) and OPDIVO + YERVOY® (ipilimumab)

OPDIVO can cause problems that can sometimes become serious or life-threatening and can lead to death. Serious side effects may include lung problems (pneumonitis); intestinal problems (colitis) that can lead to tears or holes in your intestine; liver problems (hepatitis); hormone gland problems (especially the thyroid, pituitary, adrenal glands, and pancreas); kidney problems, including nephritis and kidney failure; skin problems; inflammation of the brain (encephalitis); problems in other organs; and severe infusion reactions. Additional serious side effects observed during a separate study of YERVOY alone include: nerve problems that can lead to paralysis; and eye problems.

Important Facts About OPDIVO® (nivolumab) and OPDIVO + YERVOY® (ipilimumab)

This is a summary of important information that you need to know about OPDIVO and OPDIVO + YERVOY. Your healthcare team can work with you to help answer any questions you may have about these medications. Keep this information in a safe place so you can refer to it before and during your treatment.

Look out for the following
icons as you read:

  • Talk to your
    healthcare team
  • Call a healthcare
    provider right away
  • Helpful information
    to remember

What is OPDIVO and OPDIVO + YERVOY?

OPDIVO is a prescription medicine used to treat people who have a type of skin cancer called melanoma, and:

Whose melanoma has spread or cannot be removed by surgery (advanced melanoma).

OPDIVO can be used alone or in combination with YERVOY (OPDIVO + YERVOY).

It is not known if OPDIVO is safe and effective in children younger than 18 years of age.

OPDIVO (10 mg/mL) and YERVOY (5 mg/mL) are injections for intravenous (IV) use.


What are the serious side effects?

A serious side effect is a side effect that can sometimes become life-threatening and can lead to death. They may happen anytime during treatment or even after your treatment has ended.

OPDIVO is a medicine that may treat certain cancers by working with your immune system. OPDIVO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. Some of these problems may happen more often when OPDIVO is used in combination with YERVOY.

YERVOY can also cause serious side effects in many parts of your body which can lead to death. These problems may happen anytime during treatment with YERVOY or after you have completed treatment.

Get medical help immediately if you develop any of these symptoms or they get worse. It may keep these problems from becoming more serious. Your healthcare team will check you for side effects during treatment and may treat you with corticosteroid or hormone replacement medicines. If you have a serious side effect, your healthcare team may also need to delay or completely stop your treatment.

What are the serious side effects of OPDIVO and OPDIVO + YERVOY?

Lung problems (pneumonitis) — Things to look out for may include:

  • new or worsening cough
  • chest pain
  • shortness of breath

Intestinal problems (colitis) that can lead to tears or holes in your intestine — Things to look out for may include:

  • diarrhea (loose stools) or more
    bowel movements than usual
  • blood in your stools or dark,
    tarry, sticky stools
  • severe stomach area (abdomen)
    pain or tenderness

Liver problems (hepatitis) — Things to look out for may include:

  • yellowing of your skin or the
    whites of your eyes
  • severe nausea or vomiting
  • pain on the right side of your
    stomach area (abdomen)
  • drowsiness
  • dark urine (tea colored)
  • bleeding or bruising more easily
    than normal
  • feeling less hungry than usual
  • decreased energy

Hormone gland problems (especially the thyroid, pituitary, adrenal glands, and pancreas) — Things to look out for may include:

  • headaches that will not go away
    or unusual headaches
  • extreme tiredness
  • weight gain or weight loss
  • dizziness or fainting
  • changes in mood or behavior,
    such as decreased sex drive,
    irritability, or forgetfulness
  • hair loss
  • feeling cold
  • constipation
  • voice gets deeper
  • excessive thirst or lots of urine

Kidney problems, including nephritis and kidney failure — Things to look out for may include:

  • decrease in the amount of urine
  • blood in your urine
  • swelling in your ankles
  • loss of appetite

Skin problems — Things to look out for may include:

  • rash
  • itching
  • skin blistering
  • ulcers in the mouth or other
    mucous membranes

Inflammation of the brain (encephalitis) — Things to look out for may include:

  • headache
  • fever
  • tiredness or weakness
  • confusion
  • memory problems
  • sleepiness
  • seeing or hearing things that are not really there (hallucinations)
  • seizures
  • stiff neck

Problems in other organs — Things to look out for may include:

  • changes in eyesight
  • severe or persistent
    muscle or joint pains
  • severe muscle weakness
  • chest pain

Additional serious side effects observed during a separate study of YERVOY alone include:

Nerve problems that can lead to paralysis — Things to look out for may include:

  • unusual weakness of legs, arms, or face
  • numbness or tingling in hands or feet

Eye problems — Things to look out for may include:

  • blurry vision, double vision, or other vision problems
  • eye pain or redness

OPDIVO can cause serious side effects, including:

Severe infusion reactions — Things to look out for may include:

  • chills or shaking
  • itching or rash
  • flushing
  • difficulty breathing
  • dizziness
  • fever
  • feeling like passing out

Talk to your healthcare team right away if you get any of the symptoms of a severe infusion reaction during or after an infusion of OPDIVO.


What should I discuss with my healthcare team about pregnancy and nursing before starting treatment?

Tell your healthcare team if you are pregnant or plan to become pregnant. OPDIVO and YERVOY can harm your unborn baby. Females who are able to become pregnant should use an effective method of birth control during and for at least 5 months after the last dose of OPDIVO.

Talk to your healthcare team about birth control methods that you can use during this time. Tell your healthcare team right away if you become pregnant or think you are pregnant during treatment. You or your healthcare team should contact Bristol-Myers Squibb at 1-800-721-5072 as soon as you become aware of the pregnancy. Enrolling in a Pregnancy Safety Surveillance Study is encouraged for females who become pregnant during treatment with YERVOY. The purpose of this study is to collect information about your health and the health of your baby. You or your healthcare provider can enroll in the Pregnancy Safety Surveillance Study by calling 1-844-593-7869.

Tell your healthcare team if you are breastfeeding or plan to breastfeed. It is not known if either treatment passes into your breast milk. Do not breastfeed during treatment and for 3 months after the last dose of YERVOY.


What should I discuss with my healthcare team before starting treatment?

Talk to your healthcare team about all of your health problems or concerns, including if you:

  • have immune system problems such as autoimmune disease, Crohn’s disease, ulcerative colitis, lupus, or sarcoidosis
  • have had an organ transplant
  • have lung or breathing problems
  • have liver problems
  • have any other medical conditions

Talk to your healthcare team about all the medicines you take, including:

  • prescription medicines
  • over‑the‑counter medicines
  • vitamins
  • herbal supplements

What are the most common side effects?

The most common side effects of OPDIVO when used alone include:

  • feeling tired
  • rash
  • pain in muscles, bones, and joints
  • itchy skin
  • diarrhea
  • nausea
  • weakness
  • cough
  • vomiting
  • shortness of breath
  • constipation
  • decreased appetite
  • back pain
  • upper respiratory tract infection
  • fever
  • headache
  • abdominal pain

The most common side effects of OPDIVO when used in combination with YERVOY include:

  • feeling tired
  • rash
  • diarrhea
  • nausea
  • fever
  • pain in muscles, bones, and joints
  • upper respiratory tract infection
  • itching
  • abdominal pain
  • vomiting
  • cough
  • decreased appetite
  • shortness of breath

The most common side effects of YERVOY include:

  • feeling tired
  • diarrhea
  • nausea
  • itching
  • rash
  • vomiting
  • headache
  • weight loss
  • fever
  • decreased appetite
  • difficulty falling or staying asleep

These are not all of the possible side effects. Talk to your healthcare team for more information. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call .

For more information, please see U.S. Full Prescribing Information, including Boxed WARNING regarding immune-mediated side effects, and Medication Guide for YERVOY. Please see U.S. Full Prescribing Information and Medication Guide for OPDIVO. Talk to your healthcare team for more information about these medications.