Nivolumab And Relatlimab-Rmbw
FDA Drug Information • Also known as: Opdualag
- Brand Names
- Opdualag
- Drug Class
- Programmed Death Receptor-1 Blocking Antibody [EPC], Lymphocyte Activation Gene-3 Blocker [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Nivolumab and relatlimab-rmbw is a fixed-dose combination of two IgG4 kappa monoclonal antibodies (mAbs). Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody that has a calculated molecular mass of 146 kDa and is expressed in a recombinant Chinese Hamster Ovary (CHO) cell line. Relatlimab is a lymphocyte activation gene-3 (LAG-3) blocking antibody that has a calculated molecular mass of 148 kDa and is expressed in a recombinant CHO cell line. OPDUALAG (nivolumab and relatlimab-rmbw) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution that may contain few translucent-to-white particles. OPDUALAG is supplied as 240 mg of nivolumab and 80 mg of relatlimab in a 20 mL single-dose vial for intravenous use. Each mL of OPDUALAG 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.
What Is Nivolumab And Relatlimab-Rmbw Used For?
1 INDICATIONS AND USAGE OPDUALAG™ is indicated for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma. OPDUALAG is a combination of nivolumab, a programmed death receptor-1 (PD-1) blocking antibody, and relatlimab, a lymphocyte activation gene-3 (LAG-3) blocking antibody, indicated for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma. (1)
Dosage and Administration
2 DOSAGE AND ADMINISTRATION
Adult patients and pediatric patients 12 years of age or older who weigh at least 40 kg: 480 mg nivolumab and 160 mg relatlimab intravenously every 4 weeks. (2) Administer OPDUALAG as an intravenous infusion over 30 minutes. (2) See full Prescribing Information for dosage modifications for adverse reactions (2.2) and preparation and administration instructions for the injection (2.3) . 2.1 Recommended Dosage The recommended dosage of OPDUALAG for adult patients and pediatric patients 12 years of age or older who weigh at least 40 kg is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks until disease progression or unacceptable toxicity occurs. The recommended dosage for pediatric patients 12 years of age or older who weigh less than 40 kg has not been established [see Use in Specific Populations (8.4) ] . 2.2 Dosage Modifications No dose reduction for OPDUALAG is recommended. In general, withhold OPDUALAG for severe (Grade 3) immune-mediated adverse reactions (IMARs). Permanently discontinue OPDUALAG 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 * Based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. a 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 Adverse Reaction Severity* Dose Modification Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1) ] Pneumonitis Grade 2 Withhold a Grade 3 or 4 Permanently discontinue Colitis Grade 2 or 3 Withhold a 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 a 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 b Grade 3 or 4 Withhold until clinically stable or permanently discontinue depending on severity Nephritis...Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling.
Severe and Fatal IMARs [see Warnings and Precautions (5.1) ] Infusion-Related Reactions [see Warnings and Precautions (5.2) ] Complications of Allogeneic HSCT [see Warnings and Precautions (5.3) ] The most common adverse reactions (≥20%) are musculoskeletal pain, fatigue, rash, pruritus, and diarrhea. (6.1) The most common laboratory abnormalities (≥20%) are decreased hemoglobin, decreased lymphocytes, increased AST, increased ALT, and decreased sodium. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of OPDUALAG was evaluated in RELATIVITY-047, a randomized (1:1), double-blinded trial in 714 patients with previously untreated metastatic or unresectable melanoma [see Clinical Studies (14) ] . Patients received intravenous OPDUALAG (nivolumab 480 mg and relatlimab 160 mg) every 4 weeks (n=355) or nivolumab 480 mg by intravenous infusion every 4 weeks (n=359). Patients were treated with OPDUALAG or nivolumab until disease progression or unacceptable toxicity. The median duration of exposure was 6 months (range: 0 to 31 months) in OPDUALAG-treated patients and 5 months (range: 0 to 32 months) in nivolumab-treated patients. Serious adverse reactions occurred in 36% of patients treated with OPDUALAG. The most frequent serious adverse reactions reported in ≥1% of patients treated with OPDUALAG were adrenal insufficiency (1.4%), anemia (1.4%), colitis (1.4%), pneumonia (1.4%), acute myocardial infarction (1.1%), back pain (1.1%), diarrhea (1.1%), myocarditis (1.1%), and pneumonitis (1.1%). Fatal adverse reaction occurred in 3 (0.8%) patients who were treated with OPDUALAG; these included hemophagocytic lymphohistiocytosis, acute edema of the lung, and pneumonitis. OPDUALAG was permanently discontinued due to adverse reactions in 18% of patients. Adverse reactions which resulted in permanent discontinuation of OPDUALAG in ≥1% of patients included myocarditis (1.7%) and pneumonitis (1.4%). Dosage interruptions due to an adverse reaction occurred in 43% of patients who received OPDUALAG. Adverse reactions that required dosage interruption in ≥2% of patients who received OPDUALAG were diarrhea (3.9%), troponin increased (3.9%), AST increased (2.8%), troponin T increased (2.8%), ALT increased (2.3%), arthralgia (2.3%), hypothyroidism (2.3%), anemia (2%), fatigue (2%), pneumonitis (2%), and rash (2%). The most common (≥20%) adverse reactions that occurred in patients treated with OPDUALAG were musculoskeletal pain (45%), fatigue (39%), rash (28%), pruritus (25%), and diarrhea (24%). The most common (≥20%) laboratory abnormalities that occurred in patients treated with OPDUALAG were decreased hemoglobin (37%), decreased lymphocytes (32%), increased AST (30%), increased ALT (26%), and decreased sodium (24%). Tables 3 and 4 summarize both the adverse reactions and laboratory abnormalities, respectively, in RELATIVITY-047. Table 3: Adverse Reactions in ≥15% of Patients - RELATIVITY-047 Toxicity was graded per NCI CTCAE v5. a Includes multiple terms. Adverse Reaction OPDUALAG (n=355) Nivolumab (n=359) All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%) Musculoskeletal and Connective Tissue Musculoskeletal pain a 45 4.2 31 1.7 General Fatigue a 39 2 29 0.6 Skin and Subcutaneous Tissue Rash a 28 1.4 21 1.9 Pruritus 25 0 17 0.6 Gastrointestinal Diarrhea a 24 2 17 1.4 Nausea 17 0.6 14 0 Nervous System Headache a 18 0.3 12 0.3 Endocrine Hypothyroidism a 17 0 14 0 Metabolism and Nutrition Disorders...Contraindications
4 CONTRAINDICATIONS None.
None. (4)Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on findings in animals and mechanism of action, OPDUALAG can cause fetal harm when administered to a pregnant woman. Administration of nivolumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased abortion and premature infant death ( see Data ). Human IgG4 is known to cross the placenta; therefore, nivolumab and relatlimab have the potential to be transmitted from the mother to the developing fetus. The effects of OPDUALAG are likely to be greater during the second and third trimesters of pregnancy. There are no available data on OPDUALAG in pregnant women to evaluate a drug-associated risk. Advise the patient of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data OPDUALAG injection for intravenous use contains nivolumab and relatlimab [see Description (11) ] . Nivolumab: One function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining immune tolerance to the fetus. The effects of nivolumab on prenatal and postnatal development were evaluated in monkeys that received nivolumab twice weekly from the onset of organogenesis through delivery, at exposure levels of between 9 and 42 times higher than those observed at the clinical dose of 3 mg/kg (based on AUC). Nivolumab administration resulted in a non-dose-related increase in spontaneous abortion and increased neonatal death. In surviving infants (18 of 32 compared to 11 of 16 vehicle-exposed infants) of cynomolgus monkeys treated with nivolumab, there were no apparent malformations and no effects on neurobehavioral, immunological, or clinical pathology parameters throughout the 6-month postnatal period. Relatlimab: There are no available animal data on relatlimab. The effects of a murine surrogate anti-LAG-3 antibody was evaluated in mice using syngeneic...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING OPDUALAG (nivolumab and relatlimab-rmbw) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution for intravenous use supplied in a single-dose vial containing 240 mg of nivolumab and 80 mg of relatlimab per 20 mL (12 mg and 4 mg per mL) per carton (NDC 0003-7125-11). Store OPDUALAG refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of use. Do not freeze or shake.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.