FOR ADULTS AND CHILDREN 12 YEARS OF AGE OR OLDER WHOSE CRC HAS SPREAD TO OTHER PARTS
OF THE BODY (METASTATIC), IS MSI-H OR dMMR, AND HAS PROGRESSED AFTER TREATMENT WITH A
FLUOROPYRIMIDINE, OXALIPLATIN, AND IRINOTECAN

THE OPDIVO® (nivolumab) +
YERVOY® (ipilimumab)
COMBINATION
IMMUNOTHERAPY TEAMS
UP TO HELP FIGHT

MSI-H/dMMR METASTATIC
CRC IN PREVIOUSLY
TREATED PATIENTS

Proven in a clinical trial:

OPDIVO + YERVOY was studied in a clinical trial of 119 people whose MSI-H/dMMR CRC had spread to other parts of the body (metastatic) and who were treated with at least one prior line of therapy that would have included fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy.

  • Of the 119 people included in the clinical trial, 82 received prior treatment with all three of the following: fluoropyrimidine, oxaliplatin, and irinotecan.

    See additional information about the clinical trial below.

After treatment with a fluoropyrimidine, oxaliplatin, and irinotecan:

46% 38 of 82 people had their tumors shrink or disappear completely

  • 43% (35 of 82) saw their tumors shrink (partial response)
  • 3.7% (3 of 82) saw their tumors disappear completely (complete response)

This clinical trial is still ongoing.

The study was designed to look at overall response rate (ORR). ORR is the percentage of people who responded to treatment. These people saw their tumors either shrink (partial response) or disappear completely (complete response).

What are the serious side effects of OPDIVO when used in combination with 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 and eye problems.

What are the most common side effects of OPDIVO when used in combination with YERVOY?

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; itching; abdominal pain; vomiting; cough; decreased appetite; and shortness of breath.


Keeping your 2-phase treatment in focus

Learn how this treatment schedule helps you complete the combination treatment in 9 weeks,
followed by one monotherapy treatment.

This is a recommended schedule. Discuss any questions you have with your doctor.


OPDIVO is given through an intravenous (IV) infusion. The medicine is given directly into the bloodstream through a needle placed in a vein by a healthcare professional–usually in the arm or hand.

Talk to your doctor to learn how many treatments may be right for you. These are the recommendations about treatment, timing, and dosing. Your doctor will decide how many treatments you need. Your healthcare provider will do blood tests to check you for side effects, and may treat you with corticosteroid or hormone replacement medicines, and delay or completely stop treatment if you have side effects that are severe. Be sure to talk to your healthcare team about side effects.

Frequent communication with your healthcare team is an important part of treatment. Use your 2-week appointment to let them know how you’re feeling and ask any questions you may have. You may also be able to talk with others going through a similar situation.

If you miss an appointment, call a healthcare provider right away. Try to schedule your appointments for the same day of the week and the same time of day to make them easier to remember. It is important for you to keep all appointments with your healthcare provider.


Before you receive the OPDIVO + YERVOY combination, tell your healthcare provider if you:

  • Have immune system problems such as Crohn's disease, ulcerative colitis, lupus, or sarcoidosis
  • Have had an organ transplant
  • Have lung or breathing problems
  • Have any other medical conditions
  • 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 provider about birth control methods that you can use during this time
    • - Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment. You or your healthcare provider should contact Bristol-Myers Squibb at 1-800-721-5072 as soon as you become aware of the pregnancy
    • - Pregnancy Safety Surveillance Study: Females who become pregnant during treatment with YERVOY are encouraged to enroll in a Pregnancy Safety Surveillance Study. The purpose of this study is to collect information about the health of you and your baby. You or your healthcare provider can enroll in the Pregnancy Safety Surveillance Study by calling 1-844-593-7869
  • 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

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.


SELECT IMPORTANT FACTS ABOUT OPDIVO

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. 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; itching; abdominal pain; vomiting; cough; decreased appetite; and shortness of breath.

Important Facts About OPDIVO® (nivolumab) + 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 + YERVOY?

OPDIVO is a prescription medicine used in combination with YERVOY (OPDIVO + YERVOY) to treat colorectal cancer (a type of colon or rectal cancer). OPDIVO + YERVOY is for adults and children 12 years of age and older who:

Have colorectal cancer that has spread to other parts of the body (metastatic); AND

Have a tumor that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR); AND

Have tried treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, and it did not work or is no longer working.

OPDIVO + YERVOY was approved based on response rate and how long patients’ responses lasted. There is ongoing evaluation of clinical benefit of OPDIVO + YERVOY for this use.

It is not known if OPDIVO is safe and effective in children younger than 12 years of age with MSI-H or dMMR metastatic colorectal cancer.


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 need to delay or completely stop your treatment.

What are the serious side effects of 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
  • 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 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 .

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 of the medicines you are taking, 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 in combination with YERVOY include:

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.