Nivolumab and relatlimab-rmbw

Generic Name: nivolumab and relatlimab-rmbw
Dosage Form: injection, for intravenous use

Medically reviewed by A Rash MD. Last updated on Mar 22, 2022.

Opdualag

What is Nivolumab and relatlimab-rmbw?

Nivolumab and relatlimab-rmbw are two IgG4 kappa monoclonal antibodies that come in a fixed-dose combination (mAbs). Nivolumab is a PD-1 blocking antibody that is expressed in a recombinant Chinese Hamster ovary cell line (CHO) and has an estimated molecular mass of 146 kDa.

Nivolumab and relatlimab-rmbw injection is a sterile, preservative-free, clear to
opalescent, colorless to a slightly yellow solution that may contain few translucent-to-white
particles. Nivolumab and relatlimab-rmbwis supplied as 240 mg of nivolumab and 80 mg of relatlimab in a 20 mL
single-dose vial for intravenous use. Each mL of this solution contains 12 mg of
nivolumab, 4 mg of relatlimab, and histidine (1.1 mg), L-histidine hydrochloride monohydrate
(2.7 mg), pentetic acid (0.008 mg), polysorbate 80 (0.5 mg), sucrose (85.6 mg), and Water for
Injection, USP. The pH is 5.8.

It is used to treat:

adults and children 12 years of age or older with a type of skin cancer called melanoma that has spread or cannot be removed by surgery.

It is not known if this medicine is safe and effective when used:

in children 12 years of age or older who weigh less than 88 pounds (40 kg), or
in children younger than 12 years of age.

Important information to know

Nivolumab and relatlimab-rmbwis a drug that works with your immune system to treat melanoma, a kind of skin cancer. This can make your immune system attack healthy organs and tissues in any part of your body, causing them to malfunction. These issues can sometimes become life-threatening or even fatal. These issues can arise at any time throughout your therapy or even after it has been completed. You could be dealing with more than one of these issues at the same time.

If you notice any new or worsening symptoms, call or contact your healthcare professional right away, including:

Lung problems.

new or worsening cough
shortness of breath
chest pain

Intestinal problems.

diarrhea (loose stools) or more frequent bowel movements than usual
stool that are black, tarry, sticky, or have blood or mucus
severe stomach-area (abdominal) pain or tenderness

Liver problems.

yellowing of your skin or the whites of your eyes dark urine (tea colored)
severe nausea or vomiting
bleeding or bruising more easily than normal
pain on the right side of your stomach area (abdomen)

Hormone gland problems.

headaches that will not go away or unusual
urinating more often than usual headaches
hair loss
eye sensitivity to light
feeling cold
eye problems
constipation
rapid heartbeat
your voice gets deeper
increased sweating
dizziness or fainting
extreme tiredness
changes in mood or behavior, such as
weight gain or weight loss decreased sex drive, irritability, or forgetfulness
feeling more hungry or thirsty than usual

Kidney problems.

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

Skin problems.

rash
skin blistering or peeling
itching painful sore or ulcers in mouth or nose, throat, or genital area

Heart problems.

new or worse chest pain tiredness
irregular heartbeat or feel like your heart is racing
swelling in your ankles
shortness of breath

Problems that can also happen in other organs.

These aren’t the only signs and symptoms of immune system issues that Nivolumab and relatlimab-rmbw might cause. If you see any new or worsening signs or symptoms, call or contact your healthcare professional straight away.

Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
Persistent or severe muscle pain or weakness, muscle cramps
Low red blood cells, bruising

Getting medical treatment right away may keep these problems from becoming more serious.

During your therapy with Nivolumab and relatlimab-rmbw, your healthcare professional will check for these issues. Your doctor may prescribe corticosteroid or hormone replacement therapy for you. If you encounter severe adverse effects, your healthcare professional may need to postpone or stop your treatment with Nivolumab and relatlimab-rmbw.

Before you receive Nivolumab and relatlimab-rmbw

Tell your healthcare practitioner if you have any of the following conditions before receiving treatment:

have Crohn’s disease, ulcerative colitis, or lupus;
have undergone or plan to get an organ transplant; have received or plan to have a stem cell transplant using donor stem cells (allogeneic)
have a nervous system disorder such as myasthenia gravis or Guillain-Barré syndrome
are expecting a child or plan to have a child Nivolumab and relatlimab-rmbw can cause harm to your unborn child.

Females who are able to conceive include:

Before you begin therapy, your healthcare professional should perform a pregnancy test.
During and for at least 5 months following the final dose, you should utilize an effective method of birth control. Consult your doctor about birth control options that you can use during this period.
If you become pregnant while undergoing treatment, notify your healthcare practitioner straight away.
You are breastfeeding or intend to nurse their children. This medicine does not appear to enter into breast milk. Breastfeeding is not recommended during therapy or for 5 months after the final dosage.

How will I receive Nivolumab and relatlimab-rmbw?

Over the course of 30 minutes, your healthcare professional will inject this medicine into your vein using an intravenous (IV) line.
Nivolumab and relatlimab-rmbw is typically administered every four weeks.
The number of treatments you require will be determined by your healthcare professional.
Blood tests will be performed by your healthcare practitioner to check for adverse effects.
If you forget an appointment, phone your healthcare practitioner as soon as possible to reschedule.

Dosage and administration

Recommended Dosage

Adult patients and pediatric patients 12 years of age and older who weigh at least 40 kg should receive 480 mg nivolumab and 160 mg relatlimab intravenously every 4 weeks until disease progression or unacceptable toxicity occurs.

There is no recommended dosage for pediatric patients 12 years of age or older who weigh less than 40 kg.

Dosage Modifications

No dose reduction for Nivolumab and relatlimab-rmbw is recommended. In general, withhold Nivolumab and relatlimab-rmbw for severe (Grade 3) immune-mediated adverse reactions (IMARs). Permanently discontinue Nivolumab and relatlimab-rmbw for life-threatening (Grade 4) IMARs, recurrent severe (Grade 3) IMARs that require systemic immunosuppressive treatment, 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 adverse reactions that require management different from these general guidelines are summarized in Table 1.

Table 1: Recommended Dosage Modifications for Adverse Reactions¶

Adverse Reaction	Severity	Dose Modification
Immune-Mediated Adverse Reactions
Pneumonitis	Grade 2	Withhold
Pneumonitis	Grade 3 or 4	Permanently discontinue
Colitis	Grade 2 or 3	Withhold
Colitis	Grade 4	Permanently discontinue
Hepatitis	AST/ALT increases to more than 3 and up to 8 times ULN or Total bilirubin increases to more than 1.5 and up to 3 times ULN.	Withhold

Table 1: Recommended Dosage Modifications for Adverse Reactions

Adverse Reaction	Severity	Dose Modification
Immune-Mediated Adverse Reactions
	AST or ALT increases to more than 8 times ULN regardless of baseline. or Total bilirubin increases to more than 3 times ULN.	Permanently discontinue
Endocrinopathies	Grade 3 or 4	Withhold until clinically stable or permanently discontinue depending on severity
Nephritis with Renal Dysfunction	Grade 2 or 3 increased blood creatinine	Withhold
Nephritis with Renal Dysfunction	Grade 4 increased blood creatinine	Permanently discontinue
Exfoliative Dermatologic Conditions	Suspected SJS, TEN, or DRESS	Withhold
Exfoliative Dermatologic Conditions	Confirmed SJS, TEN, or DRESS	Permanently discontinue
Myocarditis	Grade 2, 3, or 4	Permanently discontinue
Neurological Toxicities	Grade 2	Withhold
Neurological Toxicities	Grade 3 or 4	Permanently discontinue
Other Adverse Reactions
Infusion-Related Reactions [see Warnings and Precautions (5.2)]	Grade 1 or 2	Interrupt or slow the rate of infusion
	Grade 3 or 4	Permanently discontinue

Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids. b

Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved.

ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal

Preparation and Administration

Nivolumab and relatlimab-rmbw is a fixed-dose combination of nivolumab and relatlimab.

Prior to administration, visually inspect the solution in the drug product container for particle matter and discoloration. Nivolumab and relatlimab-rmbw is a colorless to a slightly yellow solution that is transparent to opalescent.

If the solution is hazy, discolored, or includes particulate matter other than a few translucent-to-white particles, discard the bottle.

Preparation

During the preparation of the infusion solution, use an aseptic technique to assure sterility, as the product does not contain a preservative.
Nivolumab and relatlimab-rmbw can be administered diluted or undiluted and administered at a final concentration as specified in Table 2 below.
Withdraw the required volume of Nivolumab and relatlimab-rmbw and transfer it into an intravenous container. Nivolumab and relatlimab-rmbw is compatible with di(2-ethylhexyl)phthalate (DEHP)-plasticized polyvinyl chloride (PVC), ethyl vinyl acetate (EVA), and polyolefin (PO) intravenous bags.
If diluting Nivolumab and relatlimab-rmbw prior to administration:

− Dilute Nivolumab and relatlimab-rmbw solution with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to prepare an infusion meeting the final concentration and maximum infusion volume parameters as specified in Table 2 below.

− Then mix the diluted solution with gentle inversion. Do not shake.

Discard partially used vials or empty vials following infusion preparation.

Table 2: Maximum Infusion Volumes and Concentration Ranges by Patient Group

Patient Group

Maximum Infusion Volume

(mL or mL/kg)

Concentration Range (mg/mL)*

Adult patients who weigh at least 40 kg and pediatric patients 12 years of age or older who weigh at least 40 kg

160 mL

Nivolumab: 3 mg/mL to 12 mg/mL

Relatlimab: 1 mg/mL to 4 mg/mL

Adult patients who weigh less than 40 kg

4 mL/kg

Nivolumab: 3 mg/mL to 12 mg/mL

Relatlimab: 1 mg/mL to 4 mg/mL

* The concentration range in each group includes 12 mg/mL nivolumab and 4 mg/mL relatlimab as the upper limit, which represents a scenario in which the drug product is infused without dilution.

Storage of prepared solution

Store the prepared solution either:

at room temperature and room light for no more than 8 hours from the time of preparation to the end of the infusion. Discard the prepared solution if not used within 8 hours from the time of preparation;

-or- under refrigeration at 2°C to 8°C (36°F to 46°F) with protection from light for no more than 24 hours from the time of preparation, which includes the time allowed for equilibration of the infusion bag to room temperature and the duration of the infusion.

Discard the prepared solution if not used within 24 hours from the time of preparation.

Do not freeze.

Administration

Administer the infusion over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low protein binding in-line polyethersulfone (PES), nylon, or polyvinylidene fluoride (PVDF) filter (pore size of 0.2 micrometer to 1.2 micrometer).
Flush the intravenous line at the end of the infusion.
Do not coadminister other drugs through the same intravenous line.

DOSAGE FORMS AND STRENGTHS

Injection: 240 mg nivolumab and 80 mg relatlimab per 20 mL (12 mg and 4 mg per mL) as a clear to opalescent, colorless to slightly yellow solution in a single-dose vial.