OPDUALAG

Treatment must be initiated and supervised by physicians experienced in the treatment of cancer. Patients treated with Opdualag must be given the patient card and be informed about the risks of Opdualag (see also package leaflet). Posology The recommended dose for adults and adolescents 12 years of age and older is 480 mg nivolumab and 160 mg relatlimab every 4 weeks administered as an intravenous infusion over 30 minutes.

2). Treatment with Opdualag should be continued as long as clinical benefit is observed or until treatment is no longer tolerated by the patient. Dose escalation or reduction is not recommended. Dosing delay or discontinuation may be required based on individual safety and tolerability.

Guidelines for permanent discontinuation or withholding of doses are described in Table 1. Detailed guidelines for the management of immune-related adverse reactions are described in section

Summary of the safety profile Nivolumab in combination with relatlimab is associated with immune-related adverse reactions (see “Description of selected adverse reactions” below). 4. The most common adverse reactions are fatigue (41%), musculoskeletal pain (32%), rash (29%), arthralgia (26%), diarrhoea (26%), pruritus (26%), headache (20%), nausea (19%), cough (16%), decreased appetite (16%), hypothyroidism (16%), abdominal pain (14%), vitiligo (13%), pyrexia (12%), constipation (11%), urinary tract infection (11%), dyspnoea (10%), and vomiting (10%).

1%). Incidences of Grade 3-5 adverse reactions in patients with advanced (unresectable or metastatic) melanoma were 43% for nivolumab in combination with relatlimab and 35% for nivolumab treated patients. Tabulated summary of adverse reactions The safety of nivolumab in combination with relatlimab has been evaluated in 355 patients with advanced (unresectable or metastatic) melanoma (study CA224047).

94 months, are presented in Table 2. The frequencies included above and in Table 2 are based on all-cause adverse event frequencies. These reactions are presented by system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000) and not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Table 2:

Adverse reactions in clinical studies Infections and infestations Very common urinary tract infection Common upper respiratory tract infection Uncommon folliculitis Blood and lymphatic system disorders Very common anaemiaa, lymphopaeniaa, neutropaeniaa, leucopaeniaa Common thrombocytopaeniaa, eosinophilia Uncommon haemolytic anaemia Endocrine disorders Very common hypothyroidism Common adrenal insufficiency, hypophysitis, hyperthyroidism, thyroiditis Uncommon hypopituitarism, hypogonadism Metabolism and nutrition disorders Very common decreased appetite Common diabetes mellitus, hypoglycaemiaa, weight decreased, hyperuricaemia, hypoalbuminaemia, dehydration Psychiatric disorders Common confusional state Nervous system disorders Very common headache Common peripheral neuropathy, dizziness, dysgeusia Uncommon encephalitis, Guillain-Barré syndrome, optic neuritis, myasthenia gravis, Myocarditis-Myositis-Myasthenia Gravis Overlap Syndromec Eye disorders Common uveitis, visual impairment, dry eye, increased lacrimation Uncommon Vogt-Koyanagi-Harada disease, ocular hyperaemia Cardiac disorders Common myocarditis Uncommon pericardial effusion Vascular disorders Common phlebitis Respiratory, thoracic and mediastinal disorders Very common dyspnoea, cough Common pneumonitisb, nasal congestion Uncommon asthma, pleural effusion Gastrointestinal disorders Very common diarrhoea, vomiting, nausea, abdominal pain, constipation Common colitis, pancreatitis, gastritis, dysphagia, stomatitis, dry mouth Uncommon oesophagitis Rare pancreatic exocrine insufficiency Not known coeliac disease Hepatobiliary disorders Common hepatitis Uncommon cholangitis Skin and subcutaneous tissue disorders Very common rash, vitiligo, pruritus Common alopecia, lichenoid keratosis, photosensitivity reaction, dry skin Uncommon pemphigoid, psoriasis, urticaria Musculoskeletal and connective tissue disorders Very common musculoskeletal pain, arthralgia Common arthritis, muscle spasms, muscular weakness Uncommon myositis, Sjogren’s Syndrome, polymyalgia rheumatica, rheumatoid arthritis, systemic lupus erythematosus Renal and urinary disorders Common renal failure (including acute kidney injury), proteinuria Uncommon nephritis Reproductive system and breast disorders Uncommon azoospermia General disorders and administration site conditions Very common fatigue, pyrexia Common oedema, influenza-like illness, chills Rare serositis Investigations Very common increased ASTa, increased ALTa, hyponatraemiaa, increased creatininea, increased alkaline phosphatasea, hyperkalaemiaa, hypocalcaemiaa, hypomagnesaemiaa, hypercalcaemiaa, hypokalaemiaa Common increased bilirubina, hypernatraemiaa, hypermagnesaemiaa, troponin increased, gamma-glutamyl transferase increased, blood lactate dehydrogenase increased, lipase increased, amylase increased Uncommon c-reactive protein increased, red blood cell sedimentation rate increased Injury, poisoning and procedural complications Common infusion-related reaction a Frequencies of laboratory terms reflect the proportion of patients who experienced a worsening from baseline in laboratory measurements.

4. 5 and up to 3 times ULN Withhold dose(s) until laboratory values return to baseline and management with corticosteroids, if needed, is complete Immune-related hepatitis AST or ALT increases to more than 5 times ULN regardless of baseline.

or Total bilirubin increases to more than 3 times ULN or Concurrent AST or ALT increase to more than 3 times ULN and total bilirubin increase to more than 2 times ULN Permanently discontinue treatment Grade 2 or 3 creatinine elevation Withhold dose(s) until creatinine returns to baseline and management with corticosteroids is complete Immune-related nephritis and renal dysfunction Grade 4 creatinine elevation Permanently discontinue treatment Symptomatic Grade 2 or 3 hypothyroidism, hyperthyroidism, hypophysitis Grade 2 adrenal insufficiency Grade 3 diabetes Withhold dose(s) until symptoms resolve and management with corticosteroids (if needed for symptoms of acute inflammation) is complete.

0 (NCI-CTCAE v5). 4. b The safety of re-initiating Opdualag in patients previously experiencing immune-related myocarditis is not known. c Presenting as an overlap of either two or all three conditions. The most severe CTCAE grade from the individual events should be considered to assess the recommended treatment modification for Opdualag.

Special populations Paediatric population The safety and efficacy of Opdualag in children below 12 years of age have not been established. 2). 2). 2). Data from patients with severe renal impairment are too limited to draw conclusions on this population.

2). Data from patients with severe hepatic impairment are too limited to draw conclusions on this population. Method of administration Opdualag is for intravenous use only. It is to be administered as an intravenous infusion over a period of 30 minutes.

Opdualag must not be administered as an intravenous push or bolus injection. 6). 6. 1. 4 Special warnings and precautions for use Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

1.