Yervoy

Yervoy is a prescription medicine used to treat the symptoms of skin cancer (melanoma), renal cell carcinoma, hepatocellular carcinoma, non-small cell lung cancer (NSCLC), malignant pleural mesothelioma, esophageal cancer, and microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer. Yervoy may be used alone or with other medications.

Yervoy belongs to a class of drugs called antineoplastics, monoclonal antibody.

It is not known if Yervoy is safe and effective in children younger than 12 years of age.

Yervoy is a fully human monoclonal antibody that blocks T-cell inhibitory signals induced by the CTLA-4 pathway, thereby removing inhibition of the immune response with the potential for induction of immune-mediated adverse reactions.

Yervoy can 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. Some of these problems may happen more often when Yervoy is used in combination with nivolumab. Call your healthcare provider right away if you develop any of these signs or symptoms or they get worse. Do not try to treat symptoms yourself.

Intestinal problems (colitis) that can cause tears or holes (perforation) in the intestines

Signs and symptoms of colitis may include:

• diarrhea (loose stools) or more bowel movements than usual
• mucus or blood in your stools
• dark, tarry, sticky stools
• stomach pain (abdominal pain) or tenderness
• you may or may not have fever

Liver problems (hepatitis) that can lead to liver failure

Signs and symptoms of hepatitis may include:

• yellowing of your skin or the whites of your eyes
• dark urine (tea colored)
• nausea or vomiting
• pain on the right side of your stomach
• bleeding or bruise more easily than normal
• decreased energy

Skin problems that can lead to severe skin reaction

Signs and symptoms of severe skin reactions may include:

• skin rash with or without itching
• sores in your mouth
• your skin blisters or peels

Nerve problems that can lead to paralysis

Symptoms of nerve problems may include:

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

Hormone gland problems (especially the pituitary, adrenal, and thyroid glands)

Signs and symptoms that your glands are not working properly may include:

• persistent or unusual headaches
• unusual sluggishness
• feeling cold all the time
• weight gain
• changes in mood or behavior such as decreased sex drive, irritability, or forgetfulness
• dizziness or fainting Lung problems (pneumonitis).

Symptoms of pneumonitis may include:

• new or worsening cough
• chest pain
• shortness of breath Kidney problems, including nephritis and kidney failure.

Signs of kidney problems may include:

• decrease in the amount of urine
• blood in your urine
• swelling in your ankles
• loss of appetite Inflammation of the brain (encephalitis).

Signs and symptoms of encephalitis may include:

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

Eye problems

Symptoms may include:

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

Severe infusion reactions

Tell your doctor or nurse right away if you get these symptoms during an infusion of Yervoy:

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

Common side effects

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

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

The most common side effects of Yervoy when used in combination with nivolumab include:

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

These are not all of the possible side effects of Yervoy. Call your doctor for medical advice about side effects.

Patient Selection

Select patients with metastatic NSCLC for treatment with Yervoy in combination with nivolumab based on PD-L1 expression.

Information on FDA-approved tests for the determination of PD-L1 expression in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

Recommended Dosage

The recommended dosages of Yervoy as a single agent are presented in Table 1.

Table 1: Recommended Dosages for Yervoy as a Single Agent

The recommended dosages of Yervoy in combination with other therapeutic agents are presented in Table 2. Refer to the respective Prescribing Information for each therapeutic agent administered in combination with Yervoy for recommended dosage information, as appropriate.

Table 2: Recommended Dosages of Yervoy in Combination with Other Therapeutic Agents*

Recommended Dosage Modifications for Adverse Reactions

No dose reduction for Yervoy is recommended. In general, withhold Yervoy for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue Yervoy for lifethreatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, persistent moderate (Grade 2) or severe (Grade 3) reactions lasting 12 weeks or longer after last Yervoy dose (excluding endocrinopathy), or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating steroids. Dosage modifications for Yervoy or Yervoy in combination with nivolumab for adverse reactions that require management different from these general guidelines are summarized in Table 3.

When Yervoy is administered in combination with nivolumab, withhold or permanently discontinue both Yervoy and nivolumab for toxicity.

Table 3: Recommended Dosage Modifications for Adverse Reactions

Preparation and Administration

• Do not shake product.
• Visually inspect for particulate matter and discoloration prior to administration. Discard vial if solution is cloudy, there is pronounced discoloration (solution may have pale-yellow color), or there is foreign particulate matter other than translucent-to-white, amorphous particles.

Preparation of Solution

• Allow the vial(s) to stand at room temperature for approximately 5 minutes prior to preparation of infusion.
• Withdraw the required volume of Yervoy and transfer into an intravenous bag.
• Dilute with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a final concentration ranging from 1 mg/mL to 2 mg/mL. Mix diluted solution by gentle inversion.
• After preparation, store the diluted solution either refrigerated at 2°C to 8°C (36°F to 46°F) or at room temperature of 20°C to 25°C (68°F to 77°F) for no more than 24 hours from the time of preparation to the time of infusion.
• Discard partially used or empty vials of Yervoy.

Administration

• Do not co-administer other drugs through the same intravenous line.
• Flush the intravenous line with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP after each dose.
• Administer diluted solution through an intravenous line containing a sterile, non-pyrogenic, low-protein-binding in-line filter.
• When administered in combination with nivolumab, infuse nivolumab first followed by Yervoy on the same day. When administered with nivolumab and platinum-doublet chemotherapy, infuse nivolumab first followed by Yervoy and then platinum-doublet chemotherapy on the same day. Use separate infusion bags and filters for each infusion.

No formal pharmacokinetic drug interaction studies have been conducted with Yervoy.

Can cause fetal harm. Females who are able to become pregnant should use effective birth control during treatment with Yervoy and for 3 months after the last dose of Yervoy.

Do not breastfeed during treatment with Yervoy and for 3 months after the last dose of Yervoy.