• Keep this leaflet. You may need to read it again.
• It is important that you keep the patient card with you at all times.
• If you have any further questions, ask your doctor.
• If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Opdualag is and what it is used for
2. What you need to know before you are given Opdualag
3. How to use Opdualag
4. Possible side effects
5. How to store Opdualag
6. Contents of the pack and other information

• if you are allergic to nivolumab, relatlimab or any of the other ingredients of this medicine (listed in section 6). Talk to your doctor if you are not sure.

Talk to your doctor before you get Opdualag as it may cause:

• Problems with your lungs such as breathing difficulties or cough. These may be signs of inflammation of the lungs (pneumonitis or interstitial lung disease).
• Diarrhoea (watery, loose or soft stools) or inflammation of the intestines (colitis) with symptoms such as stomach pain and mucus or blood in stool.
• Inflammation of the liver (hepatitis). Signs and symptoms of hepatitis may include abnormal liver function tests, eye or skin yellowing (jaundice), pain in the right side of your stomach area, or tiredness.
• Inflammation of or problems with your kidneys. Signs and symptoms may include abnormal kidney function tests, or decrease in amount of urine.
• Problems with your hormone producing glands (including the pituitary, thyroid and adrenal glands), which may affect how these glands work. Signs and symptoms that these glands are not working properly may include fatigue (extreme tiredness), weight change or headache and visual disturbances.
• Diabetes including a serious, sometimes life-threatening problem due to acid in the blood produced from diabetes (diabetic ketoacidosis). Symptoms may include feeling more hungry or thirsty than usual, need to urinate more often, weight loss, feeling tired or having difficulty thinking clearly, breath that smells sweet or fruity, a sweet or metallic taste in your mouth, or a different odour to your urine or sweat, feeling sick or being sick, stomach pain, and deep or fast breathing.
• Inflammation of the skin that can lead to severe skin reaction (known as toxic epidermal necrolysis and Stevens-Johnson syndrome). Signs and symptoms of severe skin reaction may include rash, itching, and peeling of the skin (possibly fatal).
• Inflammation of the heart muscle (myocarditis). Signs and symptoms may include chest pain, irregular and/or rapid heartbeat, fatigue, swelling in the ankles or shortness of breath.
• Haemophagocytic lymphohistiocytosis. A rare disease in which your immune system makes too many otherwise normal infection-fighting cells called histiocytes and lymphocytes. Symptoms may include enlarged liver and/or spleen, skin rash, swollen lymph glands, breathing problems, easy bruising, kidney abnormalities, and heart problems.
• Solid organ transplant rejection.
• Graft-versus-host disease after stem cell transplantation (where the transplanted cells from a donor attack your own cells). If you have received one of these transplants, your doctor will consider whether you should receive treatment with Opdualag. Graft-versus-host disease can be severe and can lead to death.
• Infusion reactions, which may include shortness of breath, itching or rash, dizziness or fever.

Tell your doctor immediately if you have any of these signs or symptoms or if they get worse. Do not try to treat your symptoms with other medicines on your own. Your doctor may

• give you other medicines to prevent complications and reduce your symptoms,
• skip your next dose of Opdualag,
• or stop your treatment with Opdualag altogether.

Please note that these signs and symptoms are sometimes delayed and may develop weeks or months after your last dose. Before treatment, your doctor will check your general health. You will also have blood tests during your treatment.

Check with your doctor or nurse before you are given Opdualag if:

• you have an active autoimmune disease (a condition where the body attacks its own cells);
• you have melanoma of the eye;
• you have been told that your cancer has spread to your brain;
• you have been taking medicines to suppress your immune system.

Opdualag should not be used in children below 12 years of age.

Before you are given Opdualag, tell your doctor if you are taking any medicines that suppress your immune system, such as corticosteroids, since these medicines may interfere with the effect of Opdualag. However, once you are treated with Opdualag, your doctor may give you corticosteroids to reduce any possible side effects that you may have during your treatment.

Tell your doctor if you are taking, have recently taken or are planning to take any other medicines. Do not take any other medicines during your treatment without talking to your doctor first.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Do not use Opdualag if you are pregnant unless your doctor specifically tells you to. The effects of Opdualag in pregnant women are not known, but it is possible that the active substances, nivolumab and relatlimab, could harm an unborn baby.

• You must use effective contraception while you are being treated with Opdualag and for at least 5 months following the last dose of Opdualag, if you are a woman who could become pregnant.
• If you become pregnant while using Opdualag tell your doctor.

It is not known whether Opdualag can pass into breast milk and affect a baby that is breast-fed. Talk to your doctor about the benefits and risks before breast-feeding during or after treatment with Opdualag.

Opdualag has a minor influence on the ability to drive and use machines; however, use caution when performing these activities until you are sure that Opdualag does not adversely affect you.

You will also find key messages from this package leaflet on the patient card you have been given by your doctor. It is important that you keep this patient card at all times and show it to your partner or caregivers.

The recommended dose by infusion in adults and adolescents 12 years of age and older who weigh at least 30 kg is 480 mg nivolumab and 160 mg relatlimab every 4 weeks.

Depending on your dose, the appropriate amount of Opdualag may be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 50 mg/mL (5%) solution for injection before use. Opdualag may also be used undiluted.

You will receive treatment with Opdualag in a hospital or clinic, under the supervision of an experienced doctor.

Opdualag will be given to you as an infusion (a drip) into a vein, every 4 weeks. Each infusion takes about 30 minutes to give.

Your doctor will continue treating you with Opdualag for as long as you keep benefitting from it or until side effects become too severe.

It is very important for you to keep all your appointments to receive Opdualag. If you miss an appointment, ask your doctor when to schedule your next dose.

Stopping your treatment may stop the effect of the medicine. Do not stop treatment with Opdualag unless you have discussed this with your doctor.

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active substances are nivolumab and relatlimab.
  Each mL of concentrate for solution for infusion contains 12 mg of nivolumab and 4 mg of relatlimab.
  One vial of 20 mL concentrate contains 240 mg nivolumab and 80 mg relatlimab.
• The other ingredients are histidine, histidine hydrochloride monohydrate, sucrose, pentetic acid, polysorbate 80 (E433) and water for injections.

Opdualag concentrate for solution for infusion (sterile concentrate) is a clear to opalescent, colourless to slightly yellow liquid that is essentially free of particles.

It is available in cartons containing one glass vial.